WO2022174901A1

WO2022174901A1 - Catheter or cannula for treating the lung or another organ of a patient, set of catheters or cannulas and corresponding method, perfusate and combination

Info

Publication number: WO2022174901A1
Application number: PCT/EP2021/054014
Authority: WO
Inventors: Torsten Heilmann
Original assignee: ReCO2very Therapies GmbH
Current assignee: ReCO2very Therapies GmbH
Priority date: 2021-02-18
Filing date: 2021-02-18
Publication date: 2022-08-25
Anticipated expiration: 2023-08-18
Also published as: DE112021007103T5

Abstract

Described is a catheter or cannula (910a, 910b, CA5) for treating the lung (L) or another organ of a patient (P), comprising: - a lumen portion (LP) comprising a proximal end (PE) and a distal end (DE), - a proximal opening (PO) at the proximal end (PE), - a distal opening (DO) at the distal end (DE), wherein an inner lumen (L17) of the lumen portion (LP) extends from the proximal opening (PO) to the distal opening (DO), wherein the lumen portion (LP) comprises a first portion (P1) and a second portion (P2), wherein the second portion (P2) is arranged proximally to the first portion (P1), and wherein preferably the first portion (P1) carries a radially expandable arrangement that has an expanded state and a non-expanded state, the catheter or cannula (910a, 910b, CA5) is configured such that, when inserted as intended, the first portion (P1) is located in and extends into a pulmonary vein (PV) of the patient (P) and the second portion (P2) is located in and extends through the left atrium of the heart (H) of the patient (P).

Description

Catheter or cannula for treating the lung or another organ of a patient, set of catheters or cannulas and corresponding method, perfusate and combination

There are a lot of severe lung diseases that cannot be treated or healed. Even if the thorax is opened by surgery treatment may be difficult. Examples are:

- Pandemic virus infection, e.g. severe acute respiratory syndrome (SARS), e.g. CoV-1 (corona virus), CoV-2 (Covid 19) and mutations thereof, middle east respiratory syndrome (MERS-CoV),

- Chronic obstructive pulmonary disease (COPD),

- Acute respiratory distress symptom (ARDS),

- Pulmonary embolism (PE),

- Pulmonary hypertension (PHT),

- Lung fibrosis,

- Pneumonia, and

- Lung cancer.

Usually medicaments or drugs are given or administered to mitigate these diseases. Furthermore ECMO (extracorporeal membrane oxygenation), for instance VA-ECMO (veno-arterial), or ECCO2R (extracorporeal CO2 (carbon dioxide) removal) or pECLA (pumpless extracorporeal lung assist) may be performed to mitigate the symptoms. Moreover, heart assist may be applied, for instance during the treatment of the lung and or during ECMO, ECCO2R etc.

As another option, lung cancer may be treated by chemotherapy. However, it may be difficult to take the chemicals to the lung without extensive surgery and/or without detrimental systemic impacts.

In particular, the patient may suffer from a disease of the lung selected from the group consisting of or comprising cancer, COPS, ARDS and an infectious disease, for instance pneumonia or SARS. However, diseases of other organs are also contemplated in the following, especially diseases that are similar to the diseases that are mentioned above. Furthermore, the body is a complex system of organs and a disease or healing of a disease of one organ may have an impact on another organ. Thus, there is an urgent need to improve treatment of these diseases and of other diseases.

Therefore, it is an object of the present invention to disclose a catheter/cannula that makes treatment of diseases easier, especially treatment of lung diseases. Preferably, the catheter/cannula shall be appropriate for minimal invasive treatment and/or for simple surgery methods. Moreover, especially the minimal invasive treatment shall be possible without using heart support and/or lung support. Furthermore, a corresponding set of catheters/cannulas and a corresponding method shall be disclosed.

These objects are solved by the catheter/cannula of claim 1, by the set of catheters/cannulas and by the method according to the independent claims. Preferred embodiments are claimed in the sub claims.

Summary of the invention

Catheter or cannula for treating the lung or another organ of a patient, comprising:

- a lumen portion comprising a proximal end and a distal end,

- a proximal opening at the proximal end, and

- a distal opening at the distal end, wherein an inner lumen of the lumen portion extends from the proximal opening to the distal opening, wherein the lumen portion comprises a first portion and a second portion, wherein the second portion is arranged proximally to the first portion, and wherein preferably the first portion carries a radially expandable arrangement that has an expanded state and a non-expanded state, the catheter or cannula is configured such that, when inserted as intended, the first portion is located in and extends into a pulmonary vein of the patient and the second portion is located in and extends through the left atrium of the heart of the patient.

In close connection with this catheter/ cannula, the invention relates also to a perfusate comprising a medicament for use in the local treatment of a lung disease (in a patient), wherein the local treatment is restricted/limited to the lung (of the patient). The catheter/cannula is used to infuse the perfusate or the combination. Furthermore, a combination comprising the perfusate comprising a medicament and an inhalant or fluid comprising a medicament for use in the local treatment of a lung disease may be used, wherein the local treatment is restricted to the lung.

The radial extension of the radially expandable arrangement in the expanded state may be larger than the radial extension of the radially expandable arrangement in a non-expanded state, for instance at least twice or threefold as large. The lumen portion may comprise at least one wall that is circumferentially closed and that extends in a longitudinal direction. The wall may comprise a resilient material, preferably metal wire reinforced, e.g. using stainless steel. A plastic material may be uses as a resilient material, e.g. a bio compatible plastic material and/or comprise or consist of urethane, e.g. polyurethane PU and/or silicone and/or polyvinyl chloride PVC. Silicone may be used as well, e.g. using dipping technologies and subsequent curing or hardening.

The pulmonary vein catheter/cannula may be essentially straight in a basis state in which no external forces are exerted to the outer flexible tube. Alternatively, the pulmonary vein catheter/cannula may be pre-bended in order to ease insertion.

The catheter or cannula may allow perfusing the lung of a patient with a treatment liquid comprising at least one medicament/drug, especially against cancer or against a virus disease or against lung infection. A transport liquid may be used to transport the treatment liquid. Alternatively, only a transport liquid without a treatment liquid may be used for perfusion, e.g. in order to dissolve thrombus or in order to remove treatment substances which have been delivered through other ways, e.g. by inhalation. Alternatively, a perfusate as described below may be used.

The direction of perfusion through the blood vessels may be antegrade, i.e. in the natural direction, or retrograde perfusion, i.e. opposite to the natural direction. Changes of the direction during one treatment session may be advantageous.

The radially expandable arrangement of the catheter or cannula may limit a transport volume of the perfusion liquid at one end of the transport volume. Vessels and/or tissue of the organ may limit the transport volume laterally. The transport volume may be limited to only one organ or to only a part of an organ, preferably to the lung, the heart, the liver, the kidneys, the stomach, the brain, the colon, the gall bladder, the urinary bladder or the pancreas.

The optional radially expandable arrangement of the catheter or cannula may be a balloon or an expandable cage arrangement carrying a membrane which is used for sealing purposes. The cage arrangement may comprise at least 3 to 20 wires, e.g. made of metal (e.g. Nitinol (may be a registered trade mark)). The radially expandable arrangement may have at least one, at least two or all of the following functions:

- fixation of the catheter/cannula within a vein of the organ,

- sealing of the transport volume which is used for perfusion from a body fluid circuit, e.g. from the blood circuit, and

- enabling of a valve function with sealing in one direction and with allowing at least some flow in the other direction. The lumen portion may comprise a third portion that is arranged proximally of and preferably adjacent to the second portion. The catheter or cannula may be configured such that, when inserted as intended, the third portion is located in and extends along the coronary sinus vein of the heart and through a hole within the wall of the coronary sinus vein and within a wall of the left atrium. The pulmonary vein which is mentioned above may be one of the right pulmonary veins. The route via the coronary sinus vein enables to reach one or both of the right pulmonary veins using a catheter or cannula with comparably moderate deflection of the catheter or cannula. Especially, bending by more than 145 degree or more may be prevented as it would be the case if the route via the atrial septum is chosen. Moderate bending may allow e.g. higher flow rates within the catheter or canula and may ease the insertion of the catheter/cannula. It is of course also possible to reach the left pulmonary veins through the coronary sinus vein. However, large deflection of the catheter/cannula may be necessary in this case. Thus, other routes may be preferred for inserting a catheter/cannula into the left pulmonary veins, e.g. through the atrial septum as is described in more detail below. Nevertheless, the coronary sinus vein may be used also for reaching the left pulmonary veins if there are medical reasons, e.g. the atrial septum is already very weak or thin or the atrial septum is already occupied by a further catheter/cannula.

The lumen portion may comprise a fourth portion that is arranged proximally of and preferably adjacent to the third portion. The catheter or cannula may be configured such that, when inserted as intended, the fourth portion is located in and extends through the right atrium of the heart and through the superior vena cava of the patient. Thus, jugular access, subclavian access or other access from above is possible allowing better mobility of the patient if compared with a femoral access. Moreover, usage of shorter catheters/cannulas may be possible. Short catheters allow higher flow rates using moderate pressures. Moderate pressures may be advantageous if the transport liquid within the transport volume comprises e.g. blood cells. Hemolysis of red blood cells may be prevented or mitigated using lover pressures and therefore having less mechanical stress to the red blood cells, e.g. shear stress.

The length of the catheter or cannula may be in the range of 50 cm to 90 cm or in the range of 50 cm to 110 cm. Alternatively or additionally, the maximum outer diameter of the catheter or cannula at the first portion or the maximum outer diameter of the catheter or cannula may be in the range of 5 Fr (French) to 16 Fr or of 5 Fr to 19 Fr or in the range of 9 Fr to 11 Fr, e.g. 5 Fr, 6 Fr, 7 Fr, 8 Fr, 9 Fr, 10 Fr, 11 Fr, 12 Fr, 13 Fr, 14 Fr, 15 Fr, 16 Fr, 17 Fr, 18 Fr, 19 Fr, etc. Two of these catheters may be used, for instance guided within an outer tube, e.g. up to the atrial septum and within the coronary sinus vein. The outer tube may have an outer diameter in the range of 10 Fr to 19 Fr. All ranges may be valid for patients with body height of 180 cm (centimeter). Corresponding adaptions may be made for other body heights. Using the definitions given in this document, a tube with a maximal outer diameter of at least 10 Fr may be named as cannula. A tube having a maximal outer diameter of less than 10 Fr may be named as catheter. It is possible to use a cannula within coronary sinus vein if for instance only one tube is inserted into coronary sinus vein. It is an option to use two catheters within the coronary sinus vein in order to reach both right pulmonary veins. Furthermore, a cannula and a catheter may be used within the coronary sinus vein.

Alternatively, the catheter or cannula may be configured such that, when inserted as intended, the fourth portion is located in and extends through the inferior vena cava of the patient. Thus, a femoral access may be used if appropriate, e.g. because of a medical reason and or because of usage of several catheters/cannulas.

The length of the catheter or cannula may be in the range of 70 cm to 110 cm or in the range of 70 cm to 130 cm in order to enable femoral access. Alternatively or additionally, for femoral access the maximum outer diameter of the catheter or cannula at the first portion or the maximum outer diameter of the catheter or cannula, is in the range of 5 Fr to 16 Fr or of 5 Fr to 19 Fr or in the range of 9 Fr to 11 Fr, e.g. 5 Fr, 6 Fr, 7 Fr, 8 Fr, 9 Fr, 10 Fr, 11 Fr, 12 Fr, 13 Fr, 14 Fr, 15 Fr, 16 Fr, 17 Fr, 18 Fr, 19 Fr, etc. Two of these catheters may be used, for instance guided within an outer tube, e.g. up to the atrial septum and within the coronary sinus vein. The outer tube may have an outer diameter in the range of 10 Fr to 19 Fr. Thus, catheters or cannulas with greater outer diameter compared to a catheter may also be used for femoral access. All ranges may be valid for patients with body height of 180 cm (centimeter). Corresponding adaptions may be made for other body heights.

According to an alternative, the lumen portion may comprise a third portion that is arranged proximally of the second portion. The catheter or cannula may be configured such that, when inserted as intended, the third portion may be located in and may extend through the atrial septum of the heart. The pulmonary vein that is mentioned above may be one of the left pulmonary veins or the pulmonary vein is one of the right pulmonary veins. The route through the atrial septum is preferred for reaching the left pulmonary veins because the atrial openings of the left pulmonary veins are arranged opposite to the atrial septum within the left atrium. Thus, advancing a catheter or cannula from atrial septum into the left pulmonary veins is comparably easy. However, this does not mean that there may not be a situation in which the right pulmonary veins or at least one of the right pulmonary veins may be reached through the atrial septum, e.g. if the route via the coronary sinus vein is already occupied or if this route cannot be taken for a medical reason.

Also for the route via the atrial septum, the lumen portion may comprise a fourth portion that is arranged proximally of and/or adjacent to the third portion. The catheter or cannula may be configured such that, when inserted as intended, the fourth portion is located in and extends through the right atrium of the heart and through the superior vena cava of the patient. Thus, jugular, subclavian or other access from above is possible allowing mobility of the patient and/or usage of shorter catheters/cannulas.

Also for the route through the atrial septum, the length of the catheter or cannula may be in the range of 50 cm to 90 cm or in the range of 50 cm to 110 cm. Alternatively or additionally, the maximum outer diameter of the catheter or cannula at the first portion or the maximum outer diameter of the catheter or cannula, may be in the range of 5 Fr to 16 Fr or of 5 Fr to 19 Fr or in the range of 9 Fr to 11 Fr, e.g. 5 Fr, 6 Fr, 7 Fr, 8 Fr, 9 Fr, 10 Fr, 11 Fr, 12 Fr, 13 Fr, 14 Fr, 15 Fr, 16 Fr, 17 Fr, 18 Fr, 19 Fr, etc. Two of these catheters may be used, for instance guided within an outer tube, e.g. up to the atrial septum and for instance through the right atrial septum. The outer tube may have an outer diameter in the range of 15 Fr to 31 Fr. All ranges may be valid for patients with body height of 180 cm (centimeter). Corresponding adaptions may be made for other body heights. The atrial septum may allow the usage of two cannulas (at least 10 Fr outer diameter). Thus, high prefusion flow rates may be possible, e.g. more than 0.5 1/min (liter per minute) or more than 1 1/min to give only two examples. However, thinner catheters (less than 10 Fr outer diameter) may be used as well. Furthermore, a canula may be combined with a catheter using the route via atrial septum for both.

With regard to the route through the atrial septum, femoral access is also possible. Thus, the lumen portion may comprise a fourth portion that is arranged proximally of and/or adjacent to the third portion. The catheter or cannula may be configured such that, when inserted as intended, the fourth portion is located in and extends along the inferior vena cava of the patient. Thus, a femoral access may be used also for the route via the atrial septum if appropriate, e.g. because of a medical reason and or because of usage of several catheters/cannulas.

With regard to the route through the atrial septum and femoral access, the length of the catheter or cannula may be in the range of 70 cm to 110 cm or in the range of 70 cm to 130 cm. Alternatively or additionally the maximum outer diameter of the catheter or cannula at the first portion or the maximum outer diameter of the catheter or cannula may be in the range of 5 French to 16 French or of 5 French to 19 French or in the range of 9 French to 11 French, e.g. 5 Fr, 6 Fr, 7 Fr, 8 Fr, 9 Fr, 10 Fr, 11 Fr, 12 Fr, 13 Fr, 14 Fr, 15 Fr, 16 Fr, 17 Fr, 18 Fr, 19 Fr, etc. Two of these catheters may be used, for instance guided within an outer tube, e.g. up to the atrial septum and for instance through the right atrial septum. The outer tube may have an outer diameter in the range of 15 Fr to 31 Fr. All ranges may be valid for patients with body height of 180 cm (centimeter). Corresponding adaptions may be made for other body heights. The optional radially expandable arrangement may be an inflatable balloon. The catheter or cannula may comprise at least one further lumen that is coupled to the inflatable balloon, preferably in order to guide an auxiliary liquid to the balloon and from the balloon. The balloon may have a length of at least 5 mm, at least 10 mm, at least 15 mm or of at least 20 mm. Additionally or alternatively, the balloon may have a length of at most 25 mm or at most 40 mm. The balloon may comprise one of the following materials polyethylene PE, polyethylene terephthalate PET, nylon etc.

The usage of a balloon may enable fluid tight sealing or almost fluid tight sealing of the transport volume which is used for perfusion and of another body fluid circuit, for instance the blood circuit. This may enable localized delivery of medicaments and other treatment liquids and/or of transport liquids, for instance only to lung, only to one half of lung or to only one lobe of lung or to only a sub-lobe. However, alternatively a cage arrangement may be used that carries a membrane. The membrane may enclose the proximal half of the cage arrangement. Fluid tight sealing may be possible for a flow that is directed proximally, i.e. into the respective catheter/cannula. The membrane may have a valve function, allowing to pass by flow that is directed distally at the outer surface of the respective catheter/cannula. The valve function may be reduced if the membrane is stretched more in the expanded state of the expandable cage arrangement. The valve function may be used to reach advantageous effects, e.g. to reduce load to the heart etc.

An outer flexible tube may be used for enabling treating the lung or another organ of a patient. The outer flexible tube may comprise:

- a lumen portion comprising a proximal end and a distal end,

- a proximal opening at the proximal end, and

- a distal opening at the distal end, wherein an inner lumen of the lumen portion extends from the proximal opening to the distal opening, the lumen portion comprising a first portion and a second portion, wherein the first portion is arranged more distally compared to the second portion, and the outer flexible tube is configured such that, when inserted as intended, the first portion is located within the left atrium, and the second portion is arranged a) in the coronary sinus vein or b) in the atrial septum of the heart of the patient.

The outer flexible tube may be essentially straight in a basis state in which no external forces are exerted to the outer flexible tube. This may be valid for the outer flexible tube which is configured to be inserted into the coronary sinus vein (case a) and for the outer flexible tube which is configured to be inserted through the atrial septum (case b)

Alternatively, the outer flexible tube may be pre-bended. For the outer flexible tube of case a) the following may be valid:

- in the base state, a bending angle of an intermediate section (K) is at least 45° (degree) and at most 135° (degree).

For the outer flexible tube of case b) the following may be valid:

Pre-bending may ease insertion of the outer flexible tube. The same may be true for the inner catheters/cannula and/or for catheters/cannulas which are used without an outer flexible tube in order to reach pulmonary veins, e.g. at least one of the left pulmonary veins or at least one of the right pulmonary veins.

The outer flexible tube may carry a radially expandable arrangement on its distal end or on its distal portion. The radially expandable arrangement may be a balloon or an expandable cage. The expandable arrangement may have a fixation function.

The outer flexible tube may be configured such that it may enclose a catheter/cannula as mentioned above, especially a left pulmonary vein catheter/cannula or a right pulmonary vein cannula/catheter, preferably at least two of these catheters/cannulas. Usage of the outer flexible tube may ease the insertion of at least two catheters tremendously. It is possible, to use only on puncture hole within the coronary sinus vein or through the atrial septum for the outer flexible tube and to introduce at least two other catheters/cannulas through the outer flexible tube and thereby through the punctured hole, e.g. into the left atrium and possible also further. The insertion of at least two catheters/cannulas may be necessary in order to have access to several veins.

The diameter of outer flexible tube may be more than 10 Fr but less than for instance 24 Fr if used within the coronary sinus vein. The diameter of outer flexible tube may be more than 10 Fr but less than for instance 30 Fr if it is inserted through the atrial septum. However, in both cases an outer flexible tube may be used which has an outer diameter of less than 20 Fr or of less than 19 Fr, and however, e.g. more than 5 Fr to give only one example.

The invention relates also to a further catheter or cannula for treating the lung or another organ of a patient. Especially a pulmonary artery catheter or cannula for pulmonary artery access may comprise:

- a lumen portion comprising a proximal end and a distal end,

- a proximal opening at the proximal end, and

- a distal opening at the distal end, wherein an inner lumen of the lumen portion extends from the proximal opening to the distal opening, the lumen portion comprising a first portion and a second portion, wherein the second portion is arranged proximally of the first portion, and wherein preferably the first portion carries an optional radially expandable arrangement that has an expanded state and a non-exp anded state.

This further catheter/cannula may limit the transport volume at its other end. Thus, the transport volume may be completely or almost completely be isolated or separated from a body fluid circuit, e.g. from the blood circuit.

The pulmonary artery catheter/cannula may be essentially straight in a basis state in which no external forces are exerted to the outer flexible tube. Alternatively, the pulmonary artery catheter/cannula may be pre-bended in order to ease insertion.

The catheter or cannula may be configured such that, when inserted as intended, the first portion may be located in a secondary pulmonary artery of the patient or in a tertiary pulmonary artery of the patient and the second portion may be located in a primary pulmonary artery of the patient. The primary pulmonary (first level) artery extends from the pulmonary valve up to the first bifurcation of the pulmonary arteries.

A secondary pulmonary artery (second level) extends from the first bifurcation to a secondary bifurcation. A tertiary pulmonary artery (third level) extends from a secondary bifurcation to a third bifurcation, etc.

Thus, the proposed catheter/cannula may enable treatment of only one half of an organ, e.g. of lung, or of a sub-region which is less than half of the organ, less than a third or even less than quarter of an organ. Thus, dedicated medical treatment of the organ becomes feasible. Usually, the diameter of arteries decreases with higher levels. Thus, cannulas (at least 10 Fr outer diameters) may be used for lower levels. Catheters (less than 10 Fr, less than 9 Fr, etc.) may be used for higher levels. The radially expandable arrangement may be a balloon or an expandable cage arrangement carrying a membrane for sealing purposes as described already above. The cage arrangement may comprise at least 3 to 20 wires, e.g. made of metal (e.g. Nitinol (may be a registered trade mark). The radially expandable arrangement may have at least one or all of the following functions:

- fixation of the catheter/cannula within an artery of the organ,

- enabling of a valve function with sealing in one direction and with allowing at least some flow in the other direction.

The lumen portion of the further catheter/cannula may comprise a third portion that is arranged proximally of and/or adjacent to the second portion. The catheter or cannula may be configured such that, when inserted as intended, the third portion is located in and extends through the right ventricle of the heart. Thus, intravascular access is possible. Seldinger’s techniques may be used to forward the catheter/cannula along an acute angle within the right ventricle of the heart.

The lumen portion of the further catheter/cannula may comprise a fourth portion that is arranged proximally and/or adjacent to of the third portion. The catheter or cannula may be configured such that, when inserted as intended, the fourth portion is located in and extends along the right atrium of the heart and through the superior vena cava of the patient. Thus, jugular, subclavian or other access from above is possible enabling for instance mobility of patient and/or short catheters/cannulas. Short catheters allow higher flow rates using moderate pressures. Moderate pressure may be advantageous if the transport liquid within the transport volume comprises e.g. blood cells. Hemolysis of red blood cells may be prevented or mitigated using lower pressures and therefore less mechanical stress to the red blood cells may be occur, e.g. shear stress.

With regard to the further catheter/cannula and with regard to e.g. jugular access, the length of the catheter or cannula may be in the range of 60 cm to 90 cm (e.g. if the catheter/cannula is not inserted beyond a second level bifurcation of the pulmonary artery) or in the range of 90 cm to 130 cm (e.g. if the catheter/cannula is inserted beyond a second level bifurcation of the pulmonary artery). Alternatively or additionally, the maximum outer diameter of the catheter or cannula at the first portion or the maximum outer diameter of the catheter or cannula may be in the range of 5 Fr to 22 Fr or of 8 Fr to 22 Fr or in the range of 9 Fr to 22 Fr, e.g. 5 Fr, 6 Fr, 7 Fr, 8 Fr, 9 Fr, 10 Fr, 11 Fr, 12 Fr, 13 Fr, 14 Fr, 15 Fr, 16 Fr, 17 Fr, 18 Fr, 19 Fr, 20 Fr, 21 Fr, 22 Fr, etc. All ranges may be valid for instance for patients with body height of 180 cm. Corresponding adaptions may be made for other body heights. Alternatively, the further catheter or cannula may be configured such that, when inserted as intended, the fourth portion may be located in and may extend through the inferior vena cava of the patient. Thus, femoral access or other access from below is possible, e.g. because of medical reasons or because of usage of several catheters/cannulas.

If inserted femoral the length of the further catheter or cannula may be in the range of 90 cm to 120 cm (e.g. if the catheter/cannula is not inserted beyond a second level bifurcation of the pulmonary artery) or in the range of 120 cm to 160 cm (e.g. if the catheter/cannula is inserted beyond a second level bifurcation of the pulmonary artery). Alternatively or additionally, the maximum outer diameter of the catheter or cannula at the first portion or the maximum outer diameter of the catheter or cannula, is in the range of 5 Fr to 22 Fr or of 8 Fr to 22 Fr or in the range of 9 Fr to 22 Fr. All ranges may be valid for instance for patients with body height of 180 cm. Corresponding adaptions may be made for other body heights.

The optional radially expandable arrangement may be an inflatable balloon. The catheter or cannula may comprise at least one further lumen that is coupled to the inflatable balloon, preferably in order to guide an auxiliary liquid to the balloon and from the balloon. Alternatively, an expandable cage arrangement may be used that carries a membrane, e.g. at least on its proximal half.

A further aspect of the invention relates to a set of catheters/cannulas, comprising:

- at least one of a pulmonary vein catheter or cannula according to any one of the embodiments mentioned above, and

- at least one pulmonary artery catheter or cannula according to any one of the embodiments mentioned above, and preferably at least one pump, e.g. a membrane pump, a roller pump or another pump, for instance a centrifugal pump, a radial pump or a diagonal pump.

The at least one pulmonary vein catheter or cannula and the at least one pulmonary artery catheter or cannula may be connected fluidic extracorporeal, e.g. via the pump. Thus, an isolated circulation may be realized which is isolated from the blood flow of the patient. The isolated circulation circuit may comprise:

- a first fluidic tube connection between the pump and a first end of a segment of blood vessels of the lung,

- the segment of blood vessels of the lung, - a second fluidic tube connection between the pump and a second end of the segment of blood vessels of the lung, and

- an extracorporeal connection between the end of the first fluidic connection that is not connected directly connected with the segment of blood vessels of the lung and the end of the second fluidic connection that is not connected directly connected with the segment of blood vessels of the lung.

The extracorporeal connection may be realized by a pump, e.g. by a blood pump or by another pump for pumping a liquid. Of course, intracorporeal realization of the pump may be considered as well.

Instead of a circulation a single isolated pass may be realized that is also isolated from the blood circuit of the patient.

The set of catheters/cannulas may have its own medical certification, e.g. by FDA (Federal Drug Administration), TUEV (Technical Inspection Association, Germany) or DECRA (German Motor Vehicle Inspection Association) or by another certification agency of another country or region. Pumps or other devices may be included within the set. The set may enable easier usage of the invention by the physician.

The set of catheters/ cannulas may comprise in detail:

- at least one or at least two left pulmonary vein catheter(s) or cannula(s) according to any one of the embodiments mentioned above,

- at least one or at least two right pulmonary vein catheter(s) or cannula(s) according to any one of the embodiments mentioned above,

- at least one or at least two pulmonary artery catheter(s) or cannula(s) according to one of the embodiments mentioned above, and

- optionally at least one outer flexible tube as mentioned above for enclosing at least two right pulmonary vein catheters/cannulas, e.g. an outer flexible tube which is appropriate for insertion into the coronary sinus vein, and

- optionally at least one outer flexible tube as mentioned above for enclosing at least two left pulmonary artery catheters/cannulas, e.g. an outer flexible tube which is appropriate for insertion through the atrial septum.

At least one of the outer flexible tubes may be configured to be placed within the coronary sinus vein. Another one of the outer flexible tubes may be configured to be inserted through the atrial septum. The set may be used for all relevant variants of organ perfusion, e.g. of lung perfusion. A next aspect of the invention relates to a method for treating the lung or another organ of a patient. The method may comprise:

- guiding a distal portion of a catheter or cannula up to the left atrium of the heart of the patient,

- forwarding the distal portion of the catheter or cannula through the left atrium at least up to at least one of the atrial openings of the pulmonary veins within the left atrium, and

- perfusing at least one of a treatment-liquid or perfusate (as described in more detail below) for treating the lung of a patient and a transport liquid through the catheter or cannula.

The same technical effects as mentioned above for the catheters/cannulas may also apply for the proposed method. The proposed method opens at least two routes for insertion of a catheter/cannula into a pulmonary vein, preferably using a single lumen catheter having only one tip but preferably not a split tip. One route is via the atrial septum and the other route is via the coronary sinus vein and through an artificial hole within the wall between coronary sinus vein and left atrium. Other routes are possible as well.

The catheter or cannula may be a single lumen catheter or cannula having only one distal portion. Thus, insertion may be easier compared to insertion of several catheters/cannulas along the same rout or of for instance a split tip catheter/cannula which has two distal portions.

The method may comprise:

- inserting the distal portion of the catheter or cannula into the coronary sinus vein,

- guiding the distal portion of the catheter or cannula through the coronary sinus vein,

- inserting the distal portion of the catheter or cannula from the coronary sinus vein into the left atrium of the heart, and

- forwarding the distal portion of the catheter or cannula through the left atrium at least up to at least one of the atrial openings of the right pulmonary veins.

Optionally, the distal portion of the catheter or cannula may be further advanced into the opening and into the right pulmonary vein. Comparably straight forwarding of the distal portion through the left atrium into a right pulmonary vein is possible using the coronary sinus vein route. This may ease the insertion of a catheter into one of the right pulmonary veins essentially. However, as mentioned above, a route trough the coronary sinus vein into at least one of the left pulmonary veins is possible as well, for instance if other routes to the left pulmonary veins are blocked or could not be taken because of other medical reasons. The method may further comprise:

- puncturing a hole into the wall of the coronary sinus vein and through the wall of the left atrium.

RF (radio frequency) may be used to puncture the hole as is described in more detail below. Alternatively, a needle catheter or another device may be used to puncture the hole into the wall(s).

The hole may be punctured into the wall(s) before inserting the distal portion of the catheter or cannula into the coronary sinus vein. Thus, a separate device may be used to puncture the hole. However, alternatively the catheter/cannula may be adapted also to puncture a hole during its insertion, e.g. a steerable catheter/cannula combined with an RF puncturing device. A steerable catheter/cannula is described below in more detail.

The punctured hole may be arranged near the left atrium appendix, especially within a distance of less than 2 cm (centimeter) to an inner wall of the left atrium appendix or of less than 1 cm to an inner wall of the left atrium appendix. The distance may be measured from the center of the hole or from an edge of the hole that is closest to appendix to the closest wall of the left atrium appendix. This position of the hole is approximately opposite to the atrial openings of the right pulmonary veins. Thus, insertion of the catheter/cannula is facilitated.

Only one right pulmonary vein may be used for perfusion. There, may be applications for partial lung perfusion for which the usage of only one right (or even left) pulmonary catheter/cannula is sufficiently. The usage of only one catheter within the coronary sinus vein may enable the usage of larger outer diameters of the catheter/cannula compared for instance with the usage of at least two catheters within coronary sinus vein and/or it may leave more fluid volume between an outer surface of the catheter/cannula and an inner surface of the coronary sinus vein for drainage of venous blood through the coronary sinus vein to the Thebesian valve, i.e. to right atrium.

Alternatively, a distal portion of a second catheter or cannula may be guided through the coronary sinus vein into the other right pulmonary vein or into another pulmonary vein. There may be applications of lung perfusion in which the usage of at least two catheters is advantageously, for instance if a complete half of the lung, e.g. the right half has to be perfused and/or treated. As mentioned already above an outer flexible tube may be used to guide the first catheter/cannula and the second catheter/cannula through the coronary sinus vein. This may allow usage of only one punctured hole. However, two punctured holes may be used in the wall(s) of the coronary sinus vein/left atrium if no flexible outer tube is used. As a third alternative, the catheter or cannula may be a split tip catheter or cannula. Two guide wires and/or two introducer members may be used to insert the two distal tips of the split tip catheter into both right pulmonary veins using the coronary sinus vein route. Both veins are adjacent to one another or are only a small distance away from each other. Thus, a split tip catheter may fit to the anatomy of the openings of the right pulmonary veins into the left atrium. A first tip of the split tip of the catheter or cannula may be arranged within a first right pulmonary vein and a second tip of the catheter or cannula may be arranged within a second right pulmonary vein.

The distal portion of the catheter or cannula may carry an inflatable balloon or an expandable cage arrangement. A balloon may have a comparably tight sealing function compared for instance to some expandable cage arrangements.

The method may comprise:

- guiding a distal portion of a pulmonary artery catheter or cannula up to the left ventricle of the heart of the patient,

- forwarding the distal portion of the pulmonary artery catheter or cannula through the ventricular opening of the pulmonary artery at least beyond the first bifurcations of the pulmonary artery into the right pulmonary artery, and

- perfusing the at least one of the treatment-liquid for treating the lung of a patient and the transport liquid through the pulmonary artery catheter or cannula.

Thus, at least two catheters/cannulas may be used to establish a closed or almost closed transport volume or fluid circulation circuit within and/or comprising the right pulmonary blood vessel system. Both catheters may be within the same and/or restricted pulmonary blood vessel system at the same time or simultaneously, e.g. within the right pulmonary blood vessel system, within the blood vessel system of a lobe of the right half of the lung (lobe dedicated) or within the blood vessel system belonging only to a part of a lobe (sub lobe dedicated) of the right half of the lung. Single pass isolated transport volumes may be used as well within the left half of the lungs or sub portions thereof.

The method may further comprise:

- forwarding the distal portion pulmonary of the artery catheter or cannula through the ventricular opening of the pulmonary artery at least beyond the first bifurcation and further at least beyond one of the secondary bifurcations into a tertiary artery of the right pulmonary arteries. Thus, it may be possible to perfuse only a dedicated lobe of the right half of the lung or even only a dedicated sub-lobe of the lung or of the right half of the lung. This may be advantageously for diseases with local extension within the lung, e.g. cancer, thrombus, etc. or if several parts of the whole lung are treated sequentially in order to enable continuous usage of the non-treated parts for breathing.

Alternatively, the method may comprise:

- puncturing a hole into the atrial septum, and

- inserting a distal portion of the catheter or cannula through the hole in the atrial septum.

Again RF frequency or a needle may be used to puncture the hole into the atrial septum. The route that is established through the atrial septum allows straight forwarding of catheters through the left atrium of the heart into at least one of the left pulmonary veins. However, alternatively this route may also be used for forwarding of a catheter/cannula into one or the right pulmonary veins, e.g. using a steerable catheter.

Only one left pulmonary vein may be used for perfusion. There, may be applications for partial lung perfusion for which the usage of only one left (or even right) pulmonary catheter/cannula is sufficiently. The usage of only one catheter within the atrial septum may enable the usage of a smaller hole within the atrial septum. Thus, the impact to the atrial septum may be minimized.

Alternatively, a distal portion of a second catheter or cannula may be guided through the atrial septum into the other left pulmonary vein. There may be applications of lung perfusion in which the usage of at least two catheters is advantageously, for instance if a complete half of the lung, e.g. the left half has to be perfused and/or treated. As mentioned already above, an outer flexible tube may be used to guide the first catheter/cannula and the second catheter/cannula through the atrial septum. This may allow usage of only one punctured hole. However, two punctured holes may be used in atrial septum if no flexible outer tube is used. It is for instance possible to use two cannulas (each having an outer diameter of at least 10 Fr or of at least 12 Fr) which extend through the atrial septum. However, two catheters (outer diameter of less than 10 Fr or less than 9 Fr) or a combination of a cannula (at least lOFr outer diameter, e.g. at distal end) and of a catheter (less than 10 Fr outer diameter, e.g. at distal end) may be used as well.

As a third alternative, the catheter or cannula may be a split tip catheter or cannula. Both veins are adjacent to one another or are only a small distance away from each other. Thus, a split tip catheter may fit to the anatomy of the openings of the left pulmonary veins into the left atrium. A first tip of the split tip catheter or cannula may be arranged within a first left pulmonary vein and a second tip of the split tip catheter or cannula may be arranged within a second left pulmonary vein. The bifurcation of the split tip catheter/cannula may be arranged within the left atrium or within the right atrium.

A distal portion of the catheter or cannula may carry an inflatable balloon or an expandable cage arrangement for instance in order to attach the distal end (portion) of the catheter/cannula within the respective pulmonary vein, e.g. left pulmonary vein.

The method which uses a catheter within the atrial septum route may comprise:

- forwarding the distal portion of the pulmonary artery catheter through the ventricular opening of the pulmonary artery at least beyond the first bifurcation of the pulmonary artery into the left pulmonary artery, and

- perfusing the treatment liquid for treating the lung of a patient or of the transport liquid through the pulmonary artery catheter or cannula.

Thus, at least two catheters/cannulas may be used to establish a closed or almost closed transport volume or circulation circuit within and/or comprising the left pulmonary blood vessel system. Both catheters may be within the same and/or restricted pulmonary blood vessel system at the same time or simultaneously, e.g. within the left pulmonary blood vessel system, within the blood vessel system of a lobe of the left half of the lung (lobe dedicated) or within the blood vessel system belonging only to a part of a lobe (sub lobe dedicated) of the left half of the lung. Single pass isolated transport volumes may be used as well within the left half of the lungs or sub portions thereof.

The method may further comprise:

- forwarding the distal portion of the pulmonary artery catheter through the ventricular opening of the pulmonary artery at least beyond the first bifurcation and further at least beyond one of the secondary bifurcations into a tertiary artery of the left pulmonary arteries.

Thus, it may be possible to perfuse only a dedicated lobe of the left half of the lung or even only a dedicated sub-lobe of the lung or of the left half of the lung. This may be advantageously for diseases with local extension within the lung, e.g. cancer, thrombus, etc. or if several parts of the whole lung are treated sequentially in order to enable continuous usage of the non-treated parts for breathing. An embodiment of a method mentioned above for right pulmonary vein perfusion may be combined with an embodiment of method mentioned above for left pulmonary vein perfusion. The following variant may be used for instance:

- insertion of two separate catheters/cannulas into both right pulmonary veins through coronary sinus vein and at the same time (simultaneously) insertion of two separate catheters/cannulas into both left pulmonary veins through atrial septum. This may enable treatment of the whole lung. Heart support and/or lung support may be used in this constellation.

The method may comprise:

- arranging at least one substance transport channel within at least one air transport channel of the lung, e.g. by inhalation or by dropping liquid into an air transport channel of the lung, and

- applying a treatment substance through the at least one substance transport channel into a dedicated region of the lung simultaneously to the perfusing of the at least one of the treatment-liquid for treating the lung of a patient and the transport liquid through the catheter or cannula.

Thus, synergistic effects may be reached if two medicaments are used from both sides of the lung tissue. Alternatively, substances administered through the air transport channels may be removed from blood vessels immediately after diffusion into the blood vessels.

The treatment substance, e.g. inhaled, may comprise stem cells of at least one kind of tissue in the lung or a medicament against lung cancer or a medicament against a lung infection.

In the method mentioned above, a catheter or cannula according to any one of the embodiments mentioned above or a catheter or cannula set according to according to any one of the embodiments mentioned above may be used. Thus, the technical effects mentioned for the catheter(s)/cannula(s) or for the set of catheters/cannulas may be also valid for the corresponding methods.

The method may use a pulsed perfusion, e.g. within the range of 20 to 120 strokes per minute. A membrane pump or a peristaltic pump, e.g. in combination with an IABP (Intra-Aortic Balloon Pump) control console or a similar control unit using ECG signal (ElectroCardioGram) may be used to generate the strokes, preferably synchronously to the heart, e.g. for every beat, every second beat of the heart. Alternatively a continuous flow may be used allowing for instance higher pump rates. Thus, a centrifugal, radial, axial or diagonal pump may be used. A catheter or cannula according to any one of the embodiments mentioned above may be configured to be used or may be used in a method according to any one of embodiments mentioned above. Thus, the technical effects mentioned for the methods may also apply to the catheter/cannula.

A next aspect of the invention relates to a perfusate (treatment liquid) comprising a medicament for use in the local treatment of a lung disease (in a patient), wherein the local treatment is restricted/limited to the lung (of the patient).

It is preferred that the local treatment is restricted to a part of the lung.

In one embodiment, the local treatment is restricted to the left half of the lung or right half of the lung, particularly to a dedicated lobe of the left half of the lung or to a dedicated lobe of the right half of the lung, more particularly to a dedicated sub-lobe of the left half of the lung or to a dedicated sub-lobe of the right half of the lung.

It is preferred that the perfusate comprising the medicament is to be administered intravascular. Specifically, the administration is to be carried out intravascular and percutaneous. For example, the intravascular or intravascular and percutaneous administration is to be conducted through an endovascularly inserted cannula or catheter, preferably a cannula or catheter according to the aspect described above.

In one preferred embodiment, the perfusate comprising the medicament is to be administered antegrade. The antegrade administration may be through the pulmonary artery, specifically through the right ventricle of the heart. Preferably, the administration is through the left pulmonary artery or right pulmonary artery. More preferably, the administration is through the ventricular opening of the pulmonary artery (PA) at least beyond the first bifurcations (Bil ) of the pulmonary artery (PA) into the right pulmonary artery (rPA). Even more preferably, the administration is through the ventricular opening of the pulmonary artery (PA) at least beyond the first bifurcation (Bil) and further at least beyond one of the secondary bifurcations (Bi2) into a tertiary artery (1PA1, 1PA2, rPAl, rPA2) of the pulmonary arteries.

In one alternative preferred embodiment, the perfusate comprising the medicament is to be administered retrograde. The retrograde administration is preferably through at least one left pulmonary vein (1PV), more preferably two left pulmonary veins (lPVs), and/or at least one right pulmonary vein (rPV), more preferably two right pulmonary veins (rPYs), specifically trough the left atrium of the heart and more specifically through at least one of atrial septum (AS) and coronary sinus vein (CSV).

In one embodiment, the perfusate is an aqueous solution. In one preferred embodiment, the aqueous solution is blood or a salt solution. In case of blood, the blood preferably corresponds to the blood group of the patient to whom the blood is to be administered. In case of a salt solution, the salt solution is preferably a physiological salt solution.

In one preferred embodiment, the lung disease is selected from the group consisting of an Acute respiratory distress symptom (ARDS), a Chronic obstructive pulmonary disease (COPD), Pulmonary embolism (PE), Pulmonary hypertension (PHT), lung fibrosis, pneumonia, lung cancer, and an infection.

Specifically, the infection is a viral or bacterial infection. More specifically, the virus infection is an infection caused by a virus of the family of Coronaviridae, Arteriviridae, Roniviridae, or Mesoniviridae, Even more specifically, the virus of the family of Coronaviridae is selected from the group consisting of MERS-CoV and further mutations thereof, SARS-CoV and further mutations thereof, SARS-CoV-2 and further mutations thereof, and an Infectious Bronchitis Virus (IBV).

In one preferred embodiment, the medicament is selected from the group consisting of a medicament for the treatment of a Chronic obstructive pulmonary disease (COPD), a medicament for the treatment of an Acute respiratory distress symptom (ARDS), a medicament for the treatment of Pulmonary embolism (PE), a medicament for the treatment of Pulmonary hypertension (PHT), a medicament for the treatment of lung fibrosis, a medicament for the treatment of pneumonia, and a medicament for the treatment of lung cancer, and a medicament for the treatment of an infection.

Specifically, the infection is a viral or bacterial infection. More specifically, the virus infection is an infection caused by a virus of the family of Coronaviridae, Arteriviridae, Roniviridae, or Mesoniviridae, Even more specifically, the virus of the family of Coronaviridae is selected from the group consisting of MERS-CoV and mutations thereof, SARS-CoV and mutations thereof, SARS-CoV-2 and mutations thereof, and an Infectious Bronchitis Virus (IBV).

In one more preferred embodiment, the medicament is selected from the group consisting of a chemotherapeutic agent, an antiviral agent, an antibiotic, an anti-inflammatory agent, an immunomodulatory agent, an antibody, an anti-cytokinergic agent, a barrier-protective agent, a steroid, and stem cells (stem cell therapy), or is a combination thereof. In one even more preferred embodiment, the chemotherapeutic agent is selected from the group consisting of alkylating agents, anthracyclines, cytoskeletal disruptors (taxanes), epothilones, histone deacetylase inhibitors, inhibitors of topoisomerase I, inhibitors of topoisomerase II, kinase inhibitors, nucleotide analogs and precursor analogs, peptide antibiotics, platinium-based agents, retinoids and vinca alkaloids and its derivatives, or is a combination thereof.

Especially, the chemotherapeutic agent is selected from the group consisting of paclitaxel, doxorubicin, liposomal-encapsulated doxorubicin (liporubicin), 5-flurodeoxyuridine (FUDR), tumor necrosis factor alpha (TNF-a), melphalan, gemcitabine, carboplatin, cisplatin, bleomycin, imatinib, and smitomycin, or is a combination thereof.

Especially, the antiviral agent is selected from the group consisting of chloroquine, remdesivir, darunavir, favipiravir, lopinavir, and ritonavir, or is a combination thereof.

Especially, the immunomodulatory agent is selected from the group consisting of a steroid and a colchicine.

Especially, the barrier-protective agent is selected from the group consisting of angiotensin-(l-7) and sphingo sine- 1 -phosphate .

Especially, the anti-inflammatory agent is dexamethasone.

It was noted by the present inventor that with local application of high-dose immunomodulatory agents such as steroids, colchicine and/or anti-viral drugs, if necessary in combination with anti-cytokinergic biologies or antibiotics, and removal of these from the PV, avoidance and significant reduction of unnecessary systemic side effects in COVID-19 patients can be achieved.

Targeted high-dose administration of barrier-protective agents in diseases with acute endothelial or epithelial barrier loss (COVID-19, ARDS), e.g. angiotensin-(l-7) or sphingosine-1 -phosphate, is of advantage as these agents are not very suitable for systemic application due to their strong vasoactive effects. The local therapy of chronic lung diseases as described above is advantageous with drugs which usually have high systemic side effects (e.g. imatinib for reverse-remodeling in pulmonary hypertension).

The local treatment allows the use of high doses of inflammatory agents such as dexamethasone. It also allows local chemotherapy of pulmonary carcinomas and metastases.

The medicament as described above is preferably to be administered at a flow rate of between 0.25 1/min (liter per minute) to 8 1/min, preferably 0.5 1/min to 3.5 1/min, more preferably 1 1/min to 1.5 1/min. However, after injection of a bolus, it may be also possible to have a zero-flow rate during the application of the medicament/perfusate.

A next aspect of the invention relates to a combination comprising:

- a perfusate comprising a medicament, and

- an inhalant or fluid comprising a medicament for use in the local treatment of a lung disease, wherein the local treatment is restricted to the lung.

The perfusate is preferably a perfusate according to the aspect described above.

Definitions

Before the present invention is described in detail below, it is to be understood that this invention is not limited to the particular methodology, protocols and reagents described herein as these may vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to limit the scope of the present invention which will be limited only by the appended claims. Unless defined otherwise, all technical and scientific terms used herein have the same meanings as commonly understood by one of ordinary skill in the art.

Preferably, the terms used herein are defined as described in “A multilingual glossary of biotechnological terms: (IUPAC Recommendations)”, Leuenberger, H.G.W, Nagel, B. and Kolbl, H. eds. (1995), Helvetica Chimica Acta, CH-4010 Basel, Switzerland).

The term “disease”, as used herein, may refer to an abnormal condition that affects the body of an individual. A disease is often understood as a medical condition associated with specific symptoms and signs. A disease may be caused by factors originally from an external source, such as infectious disease, or it may be caused by internal dysfunctions, such as autoimmune disease. In humans, “disease” is often used more broadly to refer to any condition that causes pain, dysfunction, distress, social problems, or death to the individual afflicted, or similar problems for those in contact with the individual. In this broader sense, it sometimes includes injuries, disabilities, disorders, syndromes, infectious, isolated symptoms, deviant behaviors, and atypical variations of structure and function, while in other contexts and for other purposes these may be considered distinguishable categories. Diseases usually affect individuals not only physically, but also emotionally, as contracting and living with many diseases can alter one's perspective on life, and one's personality. In the context of the present invention, the disease may be selected from the group consisting of or comprising cancer and infectious disease.

The terms “cancer disease” or “cancer”, as used herein, may refer to or describe the physiological condition in an individual that is typically characterized by unregulated cell growth. Examples of cancers include, but are not limited to, carcinoma, lymphoma, blastoma and sarcoma. More particularly, examples of such cancers include lung cancer, liver cancer or cancer of other organs. The cancer may be selected from the group comprising or consisting of lung cancer, urothelial cancer, bladder cancer, liver cancer, kidney cancer/renal cancer, stomach cancer and brain cancer.

The term “lung disease”, as used herein, refers to a disorder affecting the lungs. The term “lung disease” includes, but is not limited to, an Acute respiratory distress symptom (ARDS), a Chronic obstructive pulmonary disease (COPD), Pulmonary embolism (PE), Pulmonary hypertension (PHT), lung fibrosis, pneumonia, lung cancer, an infection, and many other breathing problems. The infection may be a viral or bacterial infection. Specifically, the virus infection is an infection caused by a virus of the family of Coronaviridae, Arteriviridae, Roniviridae, or Mesoniviridae . More specifically, the virus of the family of Coronaviridae is selected from the group consisting of MERS-CoV, SARS-CoV, SARS-CoV-2, and an Infectious Bronchitis Virus (IBV).

The term “acute respiratory distress syndrome (ARDS)”, as used herein, refers to a type of respiratory failure characterized by rapid onset of widespread inflammation in the lungs. Symptoms may include shortness of breath (dyspnea), rapid breathing (tachypnea), and bluish skin coloration (cyanosis).

The term “chronic obstructive pulmonary disease (COPD) (also known as chronic obstructive lung disease (COLD), chronic obstructive airway disease (COAD), chronic airflow limitation (CAL) and chronic obstructive respiratory disease (CORD)”, as used herein, refers to chronic bronchitis and emphysema, a pair of commonly co-existing diseases of the lungs in which the airways become narrowed. This leads to a limitation of the flow of air to and from the lungs causing shortness of breath. In contrast to asthma, this limitation is poorly reversible and usually gets progressively worse over time. COPD is caused by noxious particles or gas, most commonly from tobacco smoking, which triggers an abnormal inflammatory response in the lung.

The term “pulmonary hypertension (PH)”, as used herein, refers to a disease characterized by an increase of blood pressure in the pulmonary artery. Pulmonary hypertension is determined as mean pulmonary artery pressure (mPAP) is > 25 mm Hg (millimeter mercury column) at rest, measured by right heart catheterization. The increase in pulmonary arterial blood pressure may lead to shortness of breath, dizziness, fainting, leg swelling., and other symptoms. Pulmonary hypertension can be a severe disease with a markedly decreased exercise tolerance (Simonneau et al. 2013). The disease may be hereditary. According to the most recent classification of the World Health Organization (WHO), pulmonary hypertension can be one of the following different types: pulmonary arterial hypertension (PAH), pulmonary hypertension due to left heart disease, pulmonary hypertension due to lung disease and/or hypoxia, chronic thromboembolic pulmonary hypertension (CTEPH), or pulmonary hypertension with unclear multifactorial mechanisms (group 5).

The term “lung cancer”, as used herein, refers to a disease which consists of uncontrolled cell growth in tissues of the lung. This growth may lead to metastasis, which is the invasion of adjacent tissue and infiltration beyond the lungs. The vast majority of primary lung cancers are carcinomas of the lung, derived from epithelial cells. Lung cancer is the most common cause of cancer-related death in men and women. The most common symptoms are shortness of breath, coughing (including coughing up blood), and weight loss. The main types of lung cancer are small cell lung carcinoma and non-small cell lung carcinoma.

The term “infectious disease”, as used herein, refers to any disease which can be transmitted from individual to individual or from organism to organism, and is caused by a microbial agent (e.g. common cold). Infectious diseases are known in the art and include, for example, a viral disease, a bacterial disease, or a parasitic disease. Said diseases are caused by a virus, a bacterium, and a parasite, respectively. In this regard, the infectious disease can be, for example, a viral or bacterial infection. Specifically, the virus infection is an infection caused by a virus of the family of Coronaviridae, Arteriviridae, Roniviridae, or Mesoniviridae. More specifically, the virus of the family of Coronaviridae is selected from the group consisting of MERS- CoV, SARS-CoV, SARS-CoV-2, and an Infectious Bronchitis Virus (IBV).

The term “perfusion”, as used herein, refers to the passage of fluid through the circulatory system or lymphatic system to an organ or a tissue. In the context of the present invention, the term “perfusion” refers to the passage of fluid through the lung, specifically part of the lung. The term “perfusate”, as used herein, refers to any fluid used in perfusion or to any fluid flowing through a tissue or organ. In the context of the present invention, the term “perfusate” preferably refers to a fluid flowing through the lung, specifically part of the lung. It preferably comprises a medicament. The perfusate comprising the medicament may alternatively be designated as treatment liquid.

The term “inhalation (from the Latin inhalare 'to breathe on')”, as used herein, refers to the intake of gaseous active ingredients or aerosols (i.e. the mixture of solid and/or liquid suspended particles and air). The most common uses in medicine are in the treatment of respiratory diseases (such as colds, sinusitis and bronchitis) and in the field of anesthesia with the administration of inhalation anesthetics as part of inhalation anesthesia. The opposite of inhalation is exhalation. In the context of the present invention, the term “inhalation” refers to the intake/passage of gaseous active ingredients or aerosols (via the mouth and/or nose) into the lung, specifically via the respiratory tract.

The term “inhalant”, as used herein, refers to gaseous and/or nebulized active ingredients or aerosols which are taken up/passaged to the lung, specifically part of the lung. The gaseous active ingredients or aerosols preferably represent a medicament. The inhalant comprising the medicament may alternatively be designated as treatment gaseous and/or nebulized medium/treatment gas.

The term “intravascular administration”, as used herein, refers to an administration of an active agent such as a medicament within a vessel or vessels. In the context of the present invention, the perfusate comprising a medicament is administered via intravascular administration to the lung, specifically part of the lung. The administration form described herein is preferably not systemic.

The term “percutaneous administration”, as used herein, refers to any medical procedure where access to inner organs or other tissue is done via needle-puncture of the skin, rather than by using an “open” approach where inner organs or tissue are exposed (typically with the use of a scalpel). The percutaneous approach is commonly used in vascular procedures. This involves a needle catheter or cannula getting access to a blood vessel, followed by the introduction of a wire through the lumen (pathway) of the needle. It is over this wire that other catheters can be placed into the blood vessel. In the context of the present invention, the perfusate comprising a medicament is administered via percutaneous administration to the lung, specifically part of the lung.

The term “antegrade administration”, as used herein, refers to the administration of an active agent, such as a medicament, through the lung, specifically part of the lung, via the pulmonary artery. Specifically, “antegrade administration” refers to a form of administration in the (natural) direction of blood circulation. The term “antegrade perfusion”, as used herein, refers to the perfusion of the lung via the pulmonary artery. Specifically, “antegrade perfusion” refers to a form of perfusion in the (natural) direction of blood circulation.

The term “retrograde administration”, as used herein, refers to the administration of an active agent, such as a medicament, through the lung, specifically part of the lung, via the (superior and/or inferior) pulmonary veins. Specifically, “retrograde administration” refers to a form of administration opposite of the (natural) blood circulation.

The term “retrograde perfusion”, as used herein, refers to the perfusion of the lung via the (superior and/or inferior) pulmonary veins. Specifically, “retrograde perfusion” refers to a form of perfusion opposite of the (natural) blood circulation.

In other words, the direction of administration/perfusion through the blood vessels may be antegrade, i.e. in the natural direction, or retrograde, i.e. opposite to the natural direction. Changes of the direction during one treatment session may be advantageous.

The terms “individual” and “subject” can be used interchangeable herein. The individual or subject may be any mammal, including both a human and another mammal, e.g. an animal. Human individuals or subjects are particularly preferred. The individual may be a patient.

The term “patient”, as used herein, may refer to any subject suffering from a disease, in particular suffering from a lung disease, such as cancer and/or an infectious disease. The patient may be treated and/or the response to said treatment may be evaluated. The patient may be any mammal, including both a human and another mammal, e.g. an animal. Human subjects as patients are particularly preferred.

The term “treatment”, in particular “therapeutic treatment”, as used herein, refers to any therapy which improves the health status and/or prolongs (increases) the lifespan of a patient. Said therapy may eliminate the disease in a patient, arrest or slow the development of a disease in a patient, inhibit or slow the development of a disease in a patient, decrease the frequency or severity of symptoms in a patient, and/or decrease the recurrence in a patient who currently has or who previously has had a disease.

A medicament/drug used in chemotherapy is a chemotherapeutic agent. The term “chemotherapeutic agent”, as used herein, may refer to a compound that is administered in the treatment of cancer. These agents or drugs are categorized by their mode of activity within a cell, for example, whether and at what stage they affect the cell cycle. Alternatively, an agent may be characterized based on its ability to directly cross-link DNA (Deoxyribonucleic Acid), to intercalate into DNA, or to induce chromosomal and mitotic aberrations by affecting nucleic acid synthesis. The chemotherapeutic agent is preferably selected from the group consisting of alkylating agents, anthracyclines, cytoskeletal disruptors (taxanes), epothilones, histone deacetylase inhibitors, inhibitors of topoisomerase I, inhibitors of topoisomerase II, kinase inhibitors, nucleotide analogs and precursor analogs, peptide antibiotics, platinium-based agents, retinoids and vinca alkaloids and its derivatives. Liquid drugs may be used.

However, usage of small balls or beads may be advantageous to deliver the medicament and/or the therapeutic substance, for instance usage of nanoballs or nanoparticles or of micro particles. Liposomes may be used as nanoparticles or as microparticles.

The term “radiation therapy (also called radiotherapy)”, as used herein, may refer to a cancer treatment that uses high doses of radiation to kill cancer cells and shrink tumors. At low doses, radiation is used in X-rays to see inside the body. At high doses, radiation therapy kills cancer cells or slows their growth by damaging their DNA. Cancer cells whose DNA is damaged beyond repair stop dividing or die. When the damaged cells die, they are broken down and removed from the body. Radiation therapy may not kill cancer cells right away. It may take days or weeks of treatment before DNA may be damaged enough for cancer cells to die. Then, cancer cells may keep dying for weeks or months after radiation therapy ends. Classical radiation by using ionizing radiation or electronic X-ray devices may be used. Alternatively, radioactive radiation may be used or radioactive substances may be brought into contact with the body, specifically with the treated organ or with a part of treated organ.

However, usage of small balls or beads may be advantageous to bring radioactive substances into the body, for instance usage of nanoballs or nanoparticles or microparticles. Liposomes may be used to produce the nanoparticles or the micro particles.

The term “extracorporeal blood/liquid”, as used herein, may refer to blood or other liquid removed/isolated from an individual’s blood or other liquid circulation.

The term “extracorporeal circuit”, as used herein, may refer to a procedure in which blood or other liquid is taken from an individual’s circulation to have a process applied to it before it is returned to the circulation. All of the system carrying the blood outside the body is termed the extracorporeal circuit. In particular, the medical agent may be suitable to be administered topically, intravenously, intra-arterially, intra-pleural, by inhalation, via a catheter, etc. The dose or more specifically the amount (size) of the dose which can be administered to a patient (“a therapeutically effective amount” or simply “an effective amount”) should be sufficient to generate a beneficial therapeutic response in the patient over time. The amount of the dose will be determined by the efficacy of the particular medical agent employed and the condition of the patient, as well as the body weight or surface area of the patient to be treated. The size of the dose also will be determined by the existence, nature, and extent of any adverse side-effects that accompany the administration of the medical, e.g. chemotherapeutic agent in a particular patient. The proposed invention may reduce adverse side-effects tremendously as the medical agent may be applied only locally and isolated from other body fluid circuits, especially form the blood circulation circuit of the body. Further factors that may be considered are the duration of contact of the tissue with the medical agent and/or how often the contact takes place. The medical agent may be administered in higher concentrations or even in much higher concentrations compared to systemic administration, i.e. to the whole body. The concentration may be raised by at least 20 percent of the dose per square meter body surface of the patient, by at least 50 percent or even by at least 100 percent.

In this application document the definition “distal” is far away from a person who inserts the catheter. “Proximal” means near to the person who inserts the catheter.

In the following the longitudinal axis of a catheter may be used as a reference axis. The terms “radial”, “axial” and/or “angularly” (circumferentially) may be used with regard to this reference axis. This may be similar to the usage of cylindrical coordinates of a cylindrical coordinate system.

The word "cannula" may refer in this application to flexible tubes or flexible pipes having an outer diameter of e.g. at least 10 Fr (3.33 mm). Liquid may be transported through the inner lumen of the cannula. The liquid transport may be the main function of the cannula.

The word "catheter" may refer in this application to medical devices comprising a flexible tube or a flexible pipe having e.g. an outer diameter of less than 10 Fr (3.33 mm). Liquid may be transported through the inner lumen of the catheter. The liquid transport may be the main function of a catheter or only an auxiliary function.

The basic principle of an endovascular catheter/cannula therapy may be a treatment of vessels and/or by using vessels for the advancement of a catheter/cannula. The catheter/cannula may comprise or be formed of (a) plastic tube(s) that may be armed with a metal. The catheter/cannula may be very flexible and may have some resiliency which enables the catheter to go back to its initial shape after external forces are removed. An incision may be made into the skin of a patient. The incision may have a length that is less than 5 cm (centimeter), less than 3 cm or less than 1 cm. Local anesthesia may be used thereby. A catheter may be used to puncture the vessel and to insert a guide-wire and/or dilators may be used to expand a punctured hole. The catheter/cannula or a further catheter/cannula may be inserted using a guide wire and/or an introducing member. Thus, no thoracotomy may be necessary.

A medicament (treatment liquid) may be comprised within a transport liquid or may form the transport liquid. Alternatively, the transport liquid may not comprise a medicament, e.g. if medicaments are delivered otherwise, for instance by inhalation or liquid drops delivered through a substance transport channel within an air channel of the lung.

The proposed method and its embodiments may not be used for treatment of the human or animal body by surgery or therapy and may not be a diagnostic method practiced on the human or animal body. Alternatively, the proposed method and its embodiments may be used for treatment of the human or animal body by surgery or therapy and may be a diagnostic method practiced on the human or animal body.

The making and using of the presently preferred embodiments are discussed in detail below. It should be appreciated, however, that the present disclosure provides many applicable concepts that can be embodied in a wide variety of specific contexts. The specific embodiments discussed are merely illustrative of specific ways to make and use the disclosed concepts, and do not limit the scope of the claims.

Moreover, same reference signs refer to the same technical features if not stated otherwise. As far as "may" is used in this application it means the possibility of doing so as well as the actual technical implementation. The present concepts of the present disclosure will be described with respect to preferred embodiments below in a more specific context namely heart and lung surgery. The disclosed concepts may also be applied, however, to other situations and/or arrangements compared to heart and/or lung surgery as well, especially to surgery of other organs.

The foregoing has outlined rather broadly the features and technical advantages of embodiments of the present disclosure. Additional features and advantages of embodiments of the present disclosure will be described hereinafter, e.g. of the subject-matter of dependent claims. It should be appreciated by those skilled in the art that the conception and specific embodiments disclosed may be readily utilized as a basis for modifying or designing other structures or processes for realizing concepts which have the same or similar purposes as the concepts specifically discussed herein. It should also be recognized by those skilled in the art that equivalent constructions do not depart from the spirit and scope of the disclosure, such as defined in the appended claims.

In the following the term “catheter” is mainly used. However, the term ’’catheter” may be replaced by the term “cannula” or by “catheter/cannula” depending on the chosen outer diameter and/or on other characteristic features which are more specific for catheters or for cannulas as mentioned above.

For a more complete understanding of the presently disclosed concepts and the advantages thereof, reference is now made to the following description in conjunction with the accompanying drawings.

The drawings are not drawn to scale. In the drawings the following is shown in:

Figure 1 A an extra corporeal circular lung perfusion blood or other liquid flow circuitry for treatment of the left half of the lung or of parts thereof,

Figure IB an embodiment of pIVLP^® (percutaneous in-vivo lung perfusion) that may be used for instance with low fluid flow,

Figure 2 a catheter/cannula that carries an inflatable expandable arrangement,

Figure 3 a split tip catheter that carries two expandable arrangements,

Figure 4 an embodiment of a lung perfusion system in combination with an inhalation system for treating for instance only one lobe of the lung (posterior view),

Figure 5 an extra corporeal circular lung perfusion blood or other liquid flow circuitry for treatment of the right half of the lung or of parts thereof,

Figure 6 a posterior view of the arrangement of figure 5,

Figure 7 an upper view of the arrangement of figure 5, and

Figure 8 a further embodiment of an extra corporeal circular lung perfusion blood or other liquid flow circuitry for treatment of the right half of the lung or of parts thereof.

Description of Figures:

The heart H of a patient P is located within his or her thorax. Patient P may be a male or female adult or a child. Heart H may comprise the following chambers:

- Right atrium RA,

- Right ventricle RV,

- Left atrium LA, and

- Left ventricle LV.

The atrial septum AS is between right atrium RA and left atrium LA. The ventricle septum VS is between right ventricle RV and left ventricle LV. The following valves of heart H are shown in the following figures:

- Tricuspid valve TV between right atrium RA and right ventricle RV,

- Mitral valve MV between left atrium LA and left ventricle LV,

- Aortic valve AV is between aorta AO and left ventricle LV, and

- Pulmonary valve PV between right ventricle RV and pulmonary artery PA.

There are two left pulmonary veins 1PV and two right pulmonary veins rPV that extend into left atrium LA of the heart H. Blood that is enriched with oxygen comes from lung L into left atrium LA through pulmonary veins PV. This is an exception in that a vein transports blood that comprises more oxygen than blood in a corresponding artery. The description of heart H will not be repeated below. However, it is clear that this description is valid for all figures which show heart H.

An isolation of lung L is reached possibly without or together with heart assist of heart H at the same time for the circuitries that use percutaneous in-vivo lung perfusion (pIVLP™^7®). Thus, isolated perfusion and/or treatment of a lung L disease may be enabled, especially antegrade fluid flow and/or retrograde fluid flow, preferably also with switching between antegrade flow and retrograde flow or between retrograde flow and antegrade flow. However, if only a part of lung L is treated, the other part(s) may function normal. There may be a lobe Lol to Lo5 (see Figure 4) dedicated treatment or treatment of only a part of a lobe Lol to Lo5 of lung L. This may also allow to treat lung L without heart H assist/support and or without lung L support, e.g. without external blood oxygenation and/or without external carbon dioxide (CO2) removal. Alternatively, partially or full heart H assist and/or lung L assist may be used even if only a part of the lung L is treated or if the whole lung L is treated at the same time.

Figure 1 A illustrates an extra corporeal lung perfusion circular blood flow circuitry 906 that may comprise three single lumen catheters 910a, 910b and 940, a pump P9 and at least one further device D9. Single lumen catheter 910a may carry a balloon arrangement Bal near its inlet port that is arranged in the upper left pulmonary vein 1PV1. Single lumen catheter 910b may carry a balloon arrangement Ba2 near its inlet port that is arranged in the lower left pulmonary vein 1PV2.

Catheter or cannula 910a, 910b for treating lung L of patient P, may comprise:

- a lumen portion LP1, LP2 comprising a proximal end PE and a distal end DE,

- a proximal opening PO at proximal end PE, and

- a distal opening D02a, D02b at distal end DE. An inner lumen of the lumen portion LP1, LP2 may extend from proximal opening PO to distal opening D02a, D02b. Lumen portion LP1, LP2 may comprise a first portion PI a, Plb and a second portion P2a, P2b. Second portion P2a, P2b may be arranged proximally to first portion Pla, Plb. First portion Pla, Plb may carry a radially expandable arrangement that has an expanded state and a non-expanded state.

Catheter or cannula 910a, 910b may be configured such that, when inserted as intended, first portion Pla, Plb is located in and extends into a pulmonary vein PV of patient P and second portion P2a, P2b is located in and extends through left atrium LA of heart H of patient P.

Lumen portion LP1, LP2 may comprise a third portion P3a, P3b that is arranged proximally of second portion P2a, P2b. Catheter or cannula 910a, 910b may be configured such that, when inserted as intended, third portion P3a, P3b is located in and extends through atrial septum AS of heart H. The pulmonary vein PV may be one of left pulmonary veins 1PV1, 1PV2 or one of right pulmonary veins rPVl, rPV2.

Lumen portion LP1, LP2 may comprise a fourth portion P4a, P4b that is arranged proximally of third portion P3a, P3b. Catheter or cannula 910a, 910b may be configured such that, when inserted as intended, the fourth portion P4a, P4b is located in and extends through right atrium RA of heart H and through superior vena cava SVC of patient P.

Third single lumen catheter 940 may have at least one outlet port within left pulmonary artery 1PA. Single lumen catheter 940 may carry a balloon arrangement Ba3 near its inlet port. Thus, the left half 1H of lung L may be treated in the illustrated example. As only a part of lung L is treated no heart H assist and/or lung L assist may be necessary.

Catheter or cannula 940 may be used for treating lung L or another organ of patient P. Thus, catheter or cannula 940 may be a pulmonary artery catheter or cannula. Catheter or cannula 940 may comprise:

- a lumen portion LP3 comprising a proximal end PE and a distal end DE,

- a proximal opening PO at proximal end PE, and

- a distal opening DO lb at distal end DE.

An inner lumen of lumen portion LP3 may extend from proximal opening PO to distal opening DO.

Lumen portion LP3 may comprise a first portion Pic and a second portion P2c. Second portion P2c may be arranged proximally of first portion Pic. First portion Pic may carry a radially expandable arrangement that has an expanded state and a non-expanded state, e.g. a balloon Ba3. Catheter or cannula 940 may be configured such that, when inserted as intended (e.g. as illustrated in Figure 1A), first portion Pic is located in a secondary pulmonary artery 1PA, rPA of patient P or in a tertiary pulmonary artery 1PA1, 1PA2, rPAl, rPA2 of patient P and second portion P2c, P2e is located in a primary pulmonary artery PA of patient P.

Lumen portion LP3 may comprise a third portion P3c that may be arranged proximally of second portion P2c. Catheter or cannula 940 may be configured such that, when inserted as intended, third portion P3c is located in and extends through right ventricle RV of heart H.

Lumen portion LP3 may comprise a fourth portion P4c that is arranged proximally of third portion P3c. Catheter or cannula 940 may be configured such that, when inserted as intended, fourth portion P4c is located in and extends along right atrium RA of heart H and through superior vena cava SVC of patient P.

Balloons Bal to Ba3 may occlude the respective blood vessels almost or fully fluid tight from the natural blood circuit BC of patient P. Thus, potentially systemic detrimental treatment substances/ medicaments/perfusates are isolated from the remainder of blood circuit BC and are only applied locally to tissue for which they have their main medical indication.

Catheter 910a may be inserted endovascularly through the left internal jugular vein IJV, superior vena cava SVC, right atrium RA, transseptal, i.e. through the atrial septum AS between right atrium RA and left atrium LA, through left atrium LA and into upper left pulmonary vein 1PV 1. A guide wire (not shown) may be used to guide catheter 910a to its final position. Alternatively, catheter 910a may be inserted through another vein. The whole blood or other liquid that enters upper left pulmonary vein 1PV1 may be taken in, i.e. drained or sucked, by catheter 910a, see arrow Ale.

Catheter 910b may be inserted endovascularly through left internal jugular vein IJV, superior vena cava SVC, right atrium RA, transseptal, i.e. through the atrial septum AS, through left atrium LA and into lower left pulmonary vein 1PV2. A further guide wire (not shown) may be used to guide catheter 910b to its final position. Alternatively, catheter 910b may be inserted through another vein. The whole blood or other liquid that enters the lower left pulmonary vein 1PV2 may be taken in, i.e. drained or sucked, by catheter 910b, see arrow A If.

The same punctured hole within atrial septum AS may be used for both catheters 910a, 910b.

Alternatively, two separate holes may be punctured within atrial septum AS. Thus a respective hole may be used for each catheter 910a, 910b.

Third single lumen catheter 940 may be inserted endovascularly through right internal jugular vein rIJV, superior vena cava SVC, right atrium RA, right ventricle RV, through pulmonary valve PV into pulmonary artery PA and further beyond the first bifurcation Bil into a secondary pulmonary artery, e.g. into left pulmonary artery 1PA. A third guide wire (not shown) may be used to guide catheter 940 to its final position. Alternatively, catheter 940 may be inserted through another vein. Almost the whole blood that comes out of catheter 940 may be injected into left pulmonary artery 1PA, see arrow Alb.

Device D9 may be an injection device that injects a medicament or a treatment substance which may be also named as perfusate, for instance for treating lung L cancer. Alternatively or additionally, device D9 may comprise a filter unit and/or a hemofiltration unit.

Further to Figure 1A, a tube 920 may be connected to the proximal ends of catheter 910a and 940b and to an inlet of pump P9. A three-port connector, e.g. a Y connector may be used thereby. An outlet of pump P9 may be connected to an inlet of device D9. A tube 930 may be connected to an outlet of device D9 and to the proximal end of catheter 940. Device D9 may be used for instance for injecting a drug or medicament or a treatment substance or treatment liquid TL into lung L of patient P.

Tubes 920, 930 may be made of a flexible material or of a more rigid material. Circuitry 906 may further include one or more blood filter units or units for dialysis of blood. It goes without saying that catheters/cannulas 910a, 910b and 940 also have an appropriate flexibility and/or resiliency.

No extra care has to be taken because all catheters/cannulas 910a, 910b and 940 are inserted into veins in which there is comparably low blood pressure compared to the blood pressure in arteries. Antegrade infusion is performed into pulmonary artery PA that has many advantages because it corresponds to the natural direction of blood flow in lung L of the patient.

The arrangement shown in Figure 1A may be used for patients P with lung L problems. Mobility of the patient is possible because no catheters are used in femoral veins or arteries. The arrangement shown in Figure 1A may be named pIVLP™'" (percutaneous in vivo lung perfusion). However, in other examples also femoral access may be used for at least one of the catheters, e.g. because of medical reasons.

In other embodiments it is possible to insert catheters 910a, 910b through right internal jugular vein rIJV or right subclavian vein to left atrium LA as described above and catheter 940 through left internal jugular vein 1IJV or left subclavian vein to left atrium LA.

Alternatively and/or additionally, device D9 may be or may comprise a CO2 (carbon dioxide) removal device, an oxygenator, etc. Furthermore, the pumping direction may be reversed in each application scenario that is mentioned above, i.e. retrograde instead of antegrade. Furthermore, it is possible to switch direction of the fluid flow once or several times.

During treatment of lung L it is possible that patient P inhales a medicament M or a treatment substance or gets this medicament M by another method via an air channel of lung L in order to promote the treatment by the substance or medicament (treatment liquid TL) that flows through the vessels of lung L and through the tissue of the alveoli. However, alternatively only medicament M may be used but not treatment liquid TL within the transport liquid. The fluid flow within circuitry 906 may comprise blood as a carrier substance. Alternatively other carrier substances may be used, for instance based on saline and/or on water.

Instead of catheters 910a, 910b only one single lumen catheter having a split tip catheter may be used, see description of Figure 3. A bifurcation Bi of the split tip catheter may be arranged e.g. within left atrium LA or within right atrium RA if the split tip catheter is in its final position.

According to a further example, it is possible to use lobe Lol to Lo5 dedicated or sub-lobe (only parts of a lobe are treated) dedicated treatment of lung L. Thus, it is possible to insert catheter 940 further beyond a secondary bifurcation Bi2 into a tertiary pulmonary artery, e.g. left pulmonary artery 1PA1. If it is for instance assumed that blood or other liquid which enters lung L through left pulmonary artery 1PA1 leaves lung L mainly or only via upper left pulmonary vein 1PV 1. Thus, a closed lung perfusion circuit may be established using only catheters 910a and 940 but not catheter 910b. Alternatively, if catheter 940 is inserted e.g. into tertiary pulmonary artery 1PA2 and if it is assumed that this artery 1PA2 is fluidically connected only with lower left pulmonary vein 1PV2, only catheter 910b may be used but not catheter 910a in order to establish a closed lung perfusion circuit.

Alternatively, catheter 940 may be inserted even deeper into the pulmonary arteries, e.g. beyond a tertiary bifurcation into a pulmonary artery of the fourth level. Alternatively or additionally, also the catheters/cannulas within the left pulmonary veins may be inserted deeper into the pulmonary veins, e.g. beyond first level bifurcations.

Furthermore, it is possible to use an outer flexible tube (not illustrated) or cannula/catheter which is used to guide catheters 910a, 910b up to the atrial septum AS. This outer flexible tube CA5 may comprise the following portions:

- an optional portion that may extend slightly within left atrium LA, e.g. less than 5 mm (millimeter) or less than 3 mm, - a portion that extends through the atrial septum AS,

- a portion that extends within right atrium RA und within superior vena cava SVC and also out of body 100 of patient, and

- an optional cage arrangement and/or balloon that prevents that the outer flexible tube slides back into right atrium RA.

Treatment of the right part of lung L is described below, see description of figures 5 to 7.

Figure IB illustrates the embodiment of figure 1A in a more schematic view illustrating further optional features. A comparably low fluid flow of for instance 0.5 liter per minute (1/min) to 1 liter per minute may be used for lung L perfusion. However, more or less fluid flow per minute is possible as well. As mentioned above, circuitry 960 may comprise or consist of:

- Single lumen catheter 940,

- Single lumen catheter 910a,

- Further single lumen catheter 910b,

- pump P9,

- An adsorber/filter unit ADSb, for instance as a part of device D9,

- A treatment substance, e.g. treatment liquid TL, delivery unit Clb, for instance as a part of device D9, and

- An optional oxygenator OXYb and/or carbon dioxide removal unit, for instance as a part of device D9.

An optional inhalation device INH may be used, e.g. for treating only the left half 1H of lung L through its air channels using a second medicament M, which may be the same medicament as within treatment liquid TL or which may be a different treatment substance. Inhalation device INH may comprise:

- A treatment substance delivery unit C2,

- An air/oxygen inlet,

- A nebulizer, and

- An inhalation tube Tu.

Bronchial dedicated inhalation is described in more detail below, see description of Figure 4. Thus, it is possible to inhale only to a treatment region TR or to an inhalation region which overlaps as close as possible with treatment region TR. Alternatively it is possible to inhale into the whole lung L. However, there may be advantages if only dedicated tissue of lung L is treated selectively from inside (blood vessels) and from outside (air channels), especially the same alveoli and/or surrounding tissue because for instance systemic effects or damage of healthy tissue may be mitigated or avoided. Localized treatment may enable that the untreated part of lung L may be used for breathing, i.e. mitigation or avoiding lung and/or heart support during treatment. Thus, blood may be pumped by heart H through right pulmonary artery rPA passing by on catheter 940 in the blood-filled space between catheter 940 and main pulmonary artery PA. Switching of the treated half and untreated half of lung L is possible as well. Furthermore, lung L may be treated in more than two different steps which are performed sequentially, e.g. in four or five sequential steps. Thus, the five lobes Lol to Lo5 of lung L may be treated one after the other.

An introducer member and/or a guide wire may be used to enable and/or to ease insertion of catheter 940. The maximum outer diameter of catheter 940 may be for instance within the range of 5 F (French) to 22 Fr. The length of catheter 940 may be in the range of 60 cm (centimeter) to 90 cm or in the range of 90 cm to 130 cm if inserted jugular or in the range of 90 cm to 120 cm or in the range of 120 cm to 160 cm if inserted femoral. All ranges may be valid for adult patients P having a body height of 180 cm. The diameter and/or length may be adapted for smaller or taller patients P correspondingly.

Single lumen catheter 940 may carry a border element at its distal end, preferably an expandable border element, for instance a balloon or a cage arrangement, preferably a cage arrangement comprising a membrane. The border element may allow the isolation of a fluid transport volume TrV that is used for treatment of lung L or of another organ from a body fluid circuit, for instance the blood circuit BC. The four chambers RA, LA, RV and LV of heart H are for instance part of blood circuit BC. The border element on catheter 940 that is not shown in Figure IB may isolate one end of transport volume TrV from blood circuit BC of patient P. Transport volume TrV may comprise or may have the following parts or portions:

- a transport volume TrVl extending from left pulmonary artery 1PA to the alveoli tissue of the alveoli of a treatment region TR which may comprise the whole left half 1H of lung L or a sub-region thereof as described below,

- a transport volume TrV2 which comprises the tissue of the corresponding alveoli in treatment region TR, and

- a transport volume TrV3 extending from the tissue of alveoli in treatment region TR to left pulmonary veins 1PV.

An air channel may be used to inflate balloon Ba3 on catheter 940, see for instance description of figure 2. An introducer member and/or a sheath member may be used to enable and/or to ease the switching of the expandable border element, e.g. balloon Ba3 or a cage, comprising a membrane from a non-expanded state that is used during insertion to an expanded state that is used for fixation of catheter 940 within left pulmonary artery 1PA. Catheter 910a may be inserted before or after catheter 940. An introducer member and/or a guide wire may be used to enable and/or to ease insertion of catheter 910a. The maximum outer diameter of catheter 910a may be for instance in the range of 5 Fr to 19 Fr. The length of catheter 910a may be in the range of 50 cm (centimeter) to 90 cm or in the range of 50 cm to 110 cm if inserted jugular or in the range of 70 cm to 110 cm or in the range of 70 cm to 130 cm if inserted femoral. All ranges may be valid for adult patients P having a body height of 180 cm. The diameter and/or length may be adapted for smaller or taller patients P correspondingly.

Catheter 910b may be inserted before or after catheter 940 and/or 910a. An introducer member and/or a guide wire may be used to enable and/or to ease insertion of catheter 910a. The maximum outer diameter of catheter 910b may be for instance in the range of 5 Fr to 19 Fr. The length of catheter 910a may be in the range of 50 cm (centimeter) to 90 cm or in the range of 50 cm to 110 cm if inserter jugular or in the range of 70 cm to 110 cm or in the range of 70 cm to 130 cm if inserted femoral. Both ranges may be valid for adult patients P having a body height of 180 cm. The lengths may be adapted for smaller or taller persons correspondingly.

Single lumen catheters 910a, 910b may carry a border element at its distal end, preferably an expandable border element, for instance balloon Bal, Ba2 or cage arrangements, preferably cage arrangements comprising a membrane. These two further border elements, e.g. balloons Bal, Ba2, may allow the isolation of fluid transport volume TrV that is used for treatment of lung L or of another organ from a body fluid circuit, for instance from blood circuit BC. The border elements (not shown in Figure IB) on catheters 910a and 910b isolate the other end of the transport volume TrV from blood circuit BC of patient P. Gas or liquid guiding channels may be used to expand or deflate balloons Bal and Ba2, see description of figure 2. Alternatively, an introducer member and/or a sheath member may be used to enable and/or to ease the switching of the expandable border element from a non-expanded state that is used during insertion to an expanded state that is used for fixation of catheters 910a, 910b. Usage of an introducer member or of a sheath may be especially appropriate for cage arrangement.

Pump P9 may pump the fluid flow through device D9, catheter 940, transport volume TrV and catheters 910a, 910b. As mentioned already above, transport volume TrV may comprise left pulmonary artery 1PA, tissue of lung L within treatment region TR and left pulmonary veins 1PV and further blood vessels located between the mentioned portions of transport volume TrV. Pump P9 may be a roller pump or another pump that allows pulsatile fluid flow. Alternatively, continuous fluid flow may be used within circuitry 960. Membrane pumps may be especially preferred due to good pumping performance and/or pumping power and/or due to less mechanical impact and/or damage to blood cells compared to other types of pumps. Adsorber/filter unit ADSb may remove a treatment substance TL and/or other particles from the fluid flow in order to allow for instance correct adjustment of concentration by delivery unit Clb. Adsorber/filter unit ADSb may be arranged downstream from pump P9 or at another appropriate position within circuitry 960.

Treatment substance delivery unit Clb may insert drugs or other treatment substances TL, preferably downstream of adsorber/filter unit ADSb. The treatment substance may be a chemotherapy substance that is mentioned in the first part of the description and/or below.

Optional oxygenator OXYb and/or carbon dioxide (CO2) removal unit may be used within circuitry 960 to adjust the oxygen level within the fluid flow. The oxygenator OXYb and/or carbon dioxide (CO2) removal unit and the adsorber/filter unit ADSb may be connected in series or in parallel fluidic connection.

Circuitry 960 may also be used for a lobe Lol to Lo5 dedicated treatment of lung L. Alternatively, only parts of a lobe Lol to Lo5 of lung L may be treated at one time. Lobe Lol to Lo5 dedicated or partially treatment of lung L may enable to use the natural function of the part of lung L that is not treated, i.e. for enriching the blood with oxygen and for removal of carbon dioxide. Thus, lung L assist may not be necessary. Even heart H assist may not be necessary as a blood flow through the untreated part of lung L is possible and afterload is reduced thereby. However, heart H assist and/or lung L assist may also be used if lung L is partially treated.

There may be the following possibilities for partial treatment of lung L, for example:

- Distal end of catheter 940 may be positioned in left pulmonary artery 1PA and distal ends of catheters 910a, 910b may be positioned in both left pulmonary veins 1PV.

- Distal end of catheter 940 may be arranged in right pulmonary artery rPA and distal ends of catheters 910a, 910b may be arranged in both right pulmonary veins rPV. However, alternative possibilities for placing catheters within at least one right pulmonary vein rPV are mentioned below, see figures 5 to 7.

- Catheter 940 may be inserted farther into the right pulmonary artery rPA or into the left pulmonary artery 1PA and/or catheter 910a and/or 910b may be inserted farther into both or one of the left pulmonary veins 1PV or right pulmonary veins rPV.

- It may be contemplated that also catheter 940 is a split tip catheter carrying two expandable border elements, e.g. for special medical applications. Furthermore, the pumping direction may be reversed in each application scenario that is mentioned above, i.e. retrograde instead of antegrade. Furthermore, it is possible to switch direction of the fluid flow once or several times.

During treatment of lung L it may be possible that patient P inhales a medicament M or treatment substance in order to promote the treatment by the substance TL or medicament that flows through the vessels of the lung L and through the tissue of the alveoli. The fluid flow within circuitry 960 may comprise blood as a carrier substance. Alternatively other carrier substances may be used, for instance based on saline and/or on water.

Figure 2 illustrates a catheter CA2 that carries an inflatable expandable arrangement, for instance a balloon Ba2a. Balloon Ba2a may have a cylindrical shape and may be connected to a distal portion of catheter CA2, for instance using an adhesive.

A channel CHI may be arranged on an outer surface of catheter CA2. Channel CHI may extend from a proximal part of catheter CA2 up to balloon Ba2a. If a fluid is driven or pumped into channel CHI balloon Ba2a inflates. If the fluid is driven out or sucked out of channel CHI then balloon Ba2a deflates. The fluid may be a liquid or a gas.

Thus, balloon Ba2a may form a border element that is between catheter CA2 and a vessel V of the blood circuit BC. Vessel V may be a pulmonary artery PA, 1PA, rPA of lung L or a pulmonary vein PV, 1PV or rPV of lung L. There may be a transport volume TrV that is used to treat lung L and that is on the distal side of inflated balloon Ba2a. The natural blood circuit BC may be on the proximal side of balloon Ba2a. Balloon Ba2a may isolate natural blood circuit BC from transport volume TrV.

Transport volume TrV may be directly in fluidic connection with catheter CA2 through the holes in a separate distal tip TP7, see for instance holes Hol7. Alternatively, catheter CA2 may have only a single end-hole EH at its distal end.

Catheter CA2 may be one of the catheters 910a, 910b, 940 or one of the other catheters mentioned in the description of the figures.

Alternatively and/or additionally, channel CHI may be arranged within catheter CA2. Catheter CA2 may be a single lumen catheter or a multi lumen catheter, especially the inner catheter or the outer catheter of a dual lumen catheter. A combination of an internal channel and an external channel CHI is possible as well. Deflated balloon Ba2a may not have a further protection shield during insertion of catheter CA2.

However, alternatively a removable sheath may be wrapped around balloon Ba2a during insertion of catheter CA2.

Alternatively a cage arrangement may be used on the distal end of lumen LI 7. This cage arrangement may comprise e.g. 3 to 20 wires. An introducer member may be used. The cage may be stretched to the non- expanded state by the introducer member and may automatically expand if the introducer member is retracted out of catheter CA2.

Figure 3 illustrates a split tip catheter CA3 that carries two expandable arrangements on its two distal end lumens L18a and L18b. An inner lumen L18 of catheter CA3 bifurcates in distal end lumen L18a and distal end lumen LI 8b at a bifurcation point or bifurcation region Bi. Each of the expandable arrangements may be realized by a balloon, see for instance balloon Ba2a as shown in Figure 2 and described above. A channel CH2 may correspond to channel CHI mentioned above. Channel CH2 may be connected to a channel CH2a that extends on distal end lumen LI 8a to the respective balloon and to a channel CH2b that extends on distal end lumen LI 8b to the respective balloon. Alternatively or additionally, internal channels may be used to inflate or deflate the balloons. A combination of an internal channel and an external channel is possible as well. Furthermore, it is possible to use two separate channels CH2al and CH2bl that extend from a proximal part of catheter LI 8 to either distal end lumen LI 8a or distal end lumen LI 8b. Separate and independent control of balloon on distal end lumen LI 8a and of balloon on distal end lumen LI 8b is possible in this variant. Introduction and fixation of catheter CA3 may be easier with separate control of both balloons.

Catheter CA3 may be a single lumen catheter having a split tip. Alternatively, catheter CA3 may comprise two separate lumens, one connected to lumen LI 8a and the other connected to lumen LI 8b.

Furthermore, for each embodiment of catheter CA3 described above catheter CA3 may not be inserted into a further catheter or may be inserted in a further catheter - thus forming a dual lumen catheter, for instance in a fixed dual lumen catheter or multi lumen catheter or non-fixed catheter dual lumen catheter or multi lumen catheter.

Alternatively two cage arrangements may be used on the distal end lumens L18a and L18b. Cage arrangements comprising 3 to 20 wires may be used. An introducer member 118 may be used that has a split tip, i.e. a bifurcation. Alternatively two separate introducer members may be used within catheter LI 8, one extending into distal end lumen LI 8a and the other extending into distal end lumen LI 8b. The introducer member(s) may be used for catheters with balloons or with cages. The cages may be stretched to the non-expanded state by the introducer member(s) and may automatically expand if the introducer member(s) are retracted out of catheter CA3.

Figure 4 illustrates an embodiment of a lung perfusion system 400 in combination with an inhalation system INH for treating only one lobe Lo5 or only one half 1H, rH of lung L, e.g. lobes Lo4 and Lo5 of left half 1H of lung L. Lung L is illustrated in a posterior view. Therefore, a left half 1H of lung L is shown on the left side of Figure 4 and a right half rH of lung L is shown on left side of Figure 4. There are the following lobes of lung L in right half rH:

- an upper lobe Lol (apical lobe),

- a middle lobe Lo2, and

- a lower lobe Lo3.

There are the following lobes of lung L in left half 1H:

- an upper lobe Lo4, and

- a lower lobe Lo5, i.e. there is no middle lobe at left half 1H of lung L.

The trachea Tr is the main air channel of lung L and extends from the throat of patient P to a bifurcation Bi4. At the bifurcation Bi4 trachea Tr branches in left primary bronchus Brla and right primary bronchus Brlb. A tube Tu may be arranged in trachea Tr and may extend through trachea Tr into left primary bronchus Brla but not into right primary bronchus Brlb or vice versa. Tube Tu may be inserted for instance through the mouth of patient P, through an incision in trachea Tr or in another way.

Primary left bronchus Brlmay have at least one further bifurcation (not shown) where it branches in secondary bronchi which branch further in tertiary bronchi and then in small bronchi of left half 1H of lung L. Primary right bronchus Brlb may have at least one further bifurcation (not shown) where it branches in secondary bronchi which branch further in tertiary bronchi and then in small bronchi of the right half rH of lung L.

An arrow Ar4 illustrates an example in which only the alveoli of left half 1H of lung L are brought into contact with a medicament M which is inhaled by patient P through tube Tu. Instead of inhalation other transport methods may be used for instance dropping a liquid into tube Tu which liquid comprises the treatment substance M. A liquid flow in the blood vessel system of lung L may be used to remove the medicament from the blood or from another auxiliary liquid, for instance saline solution. This may allow using very high doses of the medicament which is transported through at least one air channel of lung L. Although comparable high doses are used, detrimental systemic effects may be prevented or considerably mitigated by preventing uncontrolled distribution of medicament M via the blood circuit, for instance to other organs, by using the closed transport volume mentioned above. No treatment liquid TL may be used in this case within the transport liquid that flows through transport volume TrV.

This enables for instance to use stem cells in a stem cell therapy of lung L. It is prevented that the stem cells and/or other treatment substances are distributed to other organs via the blood circuit because the closed transport volume TrV is used which enables removal of the stem cells in the auxiliary liquid outside of the body. This means that no treatment substance M is introduces into the body via blood or another liquid which is transported in the closed transport volume TrV. A medicament/treatment substance is introduced or several medicaments/treatment substances M are introduced only via inhalation or another transport method through at least one air channel of lung L.

Alternatively, during treatment of lung L using a medicament TL which flows through the blood vessels of lung L it is possible that the patient inhales or gets in another way via trachea Tr a medicament M or treatment substance M in order to promote the treatment by the substance or medicament TL (or vice versa, or both) that flows within the fluid flow through the vessels of the lung L and through the tissue of the alveoli. The two treatment substances M, TL may be the same substances or may be different from each other.

In both cases, an inhalation device INH may be used that is coupled to a treatment substance delivery unit C2. Instead of inhalation other transport methods may be used for instance dropping a liquid into tube Tu which liquid comprises the treatment substance M. Air and/or oxygen O2 may be sucked into inhalation device INH in order to enable a nebulizer to generate aerosols of treatment substance M which are inhaled. Thus, the aerosols may be generated by the nebulizer. Not shown are optional valves, e.g. one way valves, etc. which may direct exhausted air into the environment or into a waste air system and which may direct inhaled air through tube Tu.

Thus, a method for treating lung L of body 100 of patient P with a pharmaceutical or therapeutic treatment substance M is described. The method may comprise:

- transporting a treatment substance M through at least one substance transport channel of lung L to only a part of the alveoli of lung L in a selected region of lung L, the substance transport channel Tu is preferably arranged within at least one air transport channel of lung L,

- while treating and/or while transporting the treatment substance M through the at least one substance transport channel Tu, transporting a liquid, for instance blood or an auxiliary liquid, through the tissue of the part of the alveoli thereby using the transport volume TrV, and/or - while treating and/ or while transporting the treatment substance M through the at least one substance transport channel Tu transporting the liquid to the outside of body 100 of which lung L is part of.

The liquid may be cleaned outside of body 100, for instance using a filter unit. The cleaned liquid may be used again in the closed transport volume TrV. Alternatively, the liquid may not be cleaned but replaced by fresh liquid. The fresh liquid (blood, auxiliary liquid, e.g. saline) may then be used in the closed transport volume TrV. If only small amounts of liquid are used, no cleaning or replacement may be necessary.

The treatment substance M may be transported to only one half 1H, rH of lung L, to only one lobe Lol to Lo5 of lung L or to only a part of a lobe (sub-lobe) Lol to Lo5 of lung L. Thus, treatment may be extended only to an area of lung L which needs treatment or which is selected by other criteria as mentioned above, e.g. sequential treatment of several parts of lung L. Healthy, areas of lung L or areas which are currently not being selected may not be treated. This may allow that the untreated areas fulfill normal lung L functions during treatment of the selected area(s) of lung L. Normal lung L functions are at least one of oxygen enhancement and carbon dioxide removal. If only small areas of lung L are treated no further lung L assist and/or heart H assist may be necessary. However, additional lung L assist and/or heart H assist may be used, especially if appropriate and/or necessary.

One of the following three variants or other variants may be used: a) Treatment substance M may be transported only to a part or to all alveoli in one selected half 1H, rH of lung L but not to non-selected alveoli in a non-selected half 1H, rH of lung L and the liquid TL may be transported in an essentially closed or in a closed transport volume TrV at least through the tissue of the selected alveoli in the selected half 1H, rH of lung L but not to alveoli in the non-selected half 1H, rH of lung L, or b) Treatment substance M may be transported only to alveoli in one selected lobe Lol to Lo5 of a selected half 1H, rH of lung L but not to non-selected lobes Lol to Lo5 of the selected half 1H, rH of lung L or only to alveoli in some selected lobes Lol to Lo5 of the selected half 1H, rH of lung L but not to a non-selected lobe Lo 1 to Lo5 in the selected half 1H, rH of lung L and the liquid TL may be transported in an essentially closed or in closed transport volume TrV at least through the tissue of the alveoli in the selected lobe Lol to Lo5 or in the selected lobes Lol to Lo5 but not through the tissue of alveoli in a non- selected half 1H, rH of lung L or in the non-selected lobes Lol to Lo5 of lung L, or c) Treatment substance M may be transported only to a first part of the alveoli of a selected lobe Lol to Lo5 of a selected half 1H, rH of lung L but not to a second part of alveoli of the selected lobe Lol to Lo5 and not to alveoli in a non-selected half 1H, rH of lung L and the treatment liquid TL may be transported in an essentially closed or in a closed transport volume TrV at least through the tissue of the first part of the alveoli in the selected half 1H, rH of lung L but not through the tissue of alveoli in the non-selected half 1H, rH of lung L of through the tissue of alveoli in the non-selected lobes Lol to Lo5 of the lung L or through the tissue of alveoli of the second part of alveoli (non-treated part).

A catheter 910a, 910b, 940 may be used for transporting a transport liquid comprising optionally treatment liquid TL. Furthermore, a method according to any one of the examples mentioned above may be used.

For all examples and variations mentioned above, treatment substance M may comprise stem cells of at least one kind of tissue in lung L. Alternatively or additionally treatment substance M may comprise a medicament against lung L cancer or a medicament against a lung L infection, for instance against a virus infection, especially a SARS (Severe Acute Respiratory Syndrome) virus infection, more specifically SARS-CoV and further mutations thereof or SARS Covid 19 and further mutations thereof, or MERS and further mutations thereof. These medicaments are mentioned in the introductory part of the description and may be the same medicaments as used for lung perfusion through the blood vessels of lung L.

Figure 5 illustrates an extra corporeal circular lung perfusion blood flow circuitry 500 comprising at least two single lumen catheters CA5a and 940b or at least three single lumen catheters CA5a, CA5b and 940b, a pump (not illustrated) and optionally at least one further device (not illustrated). The pump of circuitry 500 may correspond to pump P9 mentioned above. Further device of circuitry 500 may correspond to device D9 mentioned above. There may be the same connections between catheters CA5a, CA5b, 940b, pump and further device as mentioned above for catheters 910a, 910b, 940, pump P9 and device D9.

Catheter or cannula CA5a may be used for treating the lung L of patient P. Catheter or cannula CA5a may comprise:

- a lumen portion LP5 comprising a proximal end PE and a distal end DE5a,

- a proximal opening PO at proximal end PE, and

- a distal opening D05a at distal end DE5a.

Inner lumen of lumen portion LP5 may extend from proximal opening PO to distal opening D05a. Lumen portion LP5 may comprise a first portion Pld and a second portion P2d. Second portion P2d may be arranged proximally to first portion Pld. First portion Pld may carry a radially expandable arrangement that has an expanded state and a non-expanded state, e.g. a balloon Ba5. Catheter or cannula CA5a may be configured such that, when inserted as intended (e.g. as illustrated in Figure 5), first portion Pld is located in and extends into a pulmonary vein PV of patient P and second portion P2d is located in and extends through left atrium LA of heart H of patient P. Lumen portion LP5 may comprise a third portion P3d that is arranged proximally of second portion P2d. Catheter or cannula CA5a may be configured such that, when inserted as intended, third portion P3d is located in and extends along coronary sinus vein CSV of heart H and through a hole HI within the wall of coronary sinus vein CSV and within a wall of left atrium LA. The pulmonary vein PV may be one of the right pulmonary veins rPVl, rPV2.

Lumen portion LP5 may comprise a fourth portion P4d that is arranged proximally of third portion P3d. Catheter or cannula CA5a may be configured such that, when inserted as intended, fourth portion P4d is located in and extends through right atrium RA of heart H and through superior vena cava SVC of patient P.

The maximum outer diameter of catheter CA5a may be for instance in the range of 5 Fr to 19 Fr. The length of catheter CA5a may be in the range of 50 cm (centimeter) to 90 cm or in the range of 50 cm to 110 cm if inserted jugular or in the range of 70 cm to 110 cm or in the range of 70 cm to 130 cm if inserted femoral. All ranges may be valid for adult patients P having a body height of 180 cm. The diameter and/or length may be adapted for smaller or taller patients P correspondingly.

Catheter or cannula 940b may be used for treating lung L or another organ of patient P. Catheter or cannula 940b may be a pulmonary artery catheter or cannula. Catheter or cannula 940b may comprise:

- a lumen portion comprising a proximal end PE and a distal end DE,

- a proximal opening PO at proximal end PE, and

- a distal opening DO at distal end DE.

An inner lumen of the lumen portion of catheter or cannula 940b may extend from proximal opening PO to distal opening DO. The lumen portion of catheter or cannula 940b may comprise a first portion Pie and a second portion P2e. Second portion P2e may be arranged proximally of first portion Pie. First portion Pie may carry a radially expandable arrangement that has an expanded state and a non-expanded state. Catheter or cannula 940b may be configured such that, when inserted as intended, first portion Pie is located in a secondary pulmonary artery 1PA, rPA of patient P or in a tertiary pulmonary artery 1PA1, 1PA2, rPAl, rPA2 of patient P and second portion P2e is located in a primary pulmonary artery PA of patient P.

The lumen portion of catheter or cannula 940b may comprise a third portion P3e that is arranged proximally of second portion P2e. Catheter or cannula 940b may be configured such that, when inserted as intended, third portion P3e is located in and extends through right ventricle RV of heart H. The lumen portion of catheter or cannula 940b may comprise a fourth portion P4e that is arranged proximally of third portion P3e. Catheter or cannula 940b may be configured such that, when inserted as intended, fourth portion P4e is located in and extends along right atrium RA of heart H and through superior vena cava SVC of patient P.

The maximum outer diameter of catheter 940b may be for instance in the range of 5 Fr to 22 Fr. The length of catheter 940b may be in the range of 60 cm (centimeter) to 190 cm or in the range of 90 cm to 130 cm if inserted jugular or in the range of 90 cm to 120 cm or in the range of 120 to 160 cm if inserted femoral. All ranges may be valid for adult patients P having a body height of 180 cm. The diameter and/or length may be adapted for smaller or taller persons correspondingly.

Catheter CA5a may be inserted into the coronary sinus vein CSV, for instance percutaneous via the inferior vena cava IVC or via the superior vena cava SVC or in another appropriate way. CatheterCA5a may be further inserted through a puncture that has been established between the coronary sinus CSV and the left atrium LA. An auxiliary device may be used in order to prevent undesired blood flow from the left atrium LA or from the coronary sinus vein CSV into body 100 of patient P, for instance a small pipe or another kind of adapter device, e.g. after pulling back all catheters/cannulas or tubes from coronary sinus vein CSV. Alternatively, no such auxiliary device may be used. There may enough blood-filled space between the outer wall of catheter CA5a and inner wall of coronary sinus vein CSV in order to enable the natural drainage of blood from muscles of heart H through coronary veins into coronary sinus vein CSV and further into inferior vena cava IVC /right atrium RA.

Thus, a hole HI may be punctured which connects the inner lumen of coronary sinus vein CSV and inner lumen of left atrium LA. Hole HI may be located near left atrium appendix LAApp. Hole HI may be located at the opposite side of left atrium LA compared to the location of the atrial openings of the right pulmonary veins rPVl and rPV2. This may enable that the distal portion DP5a of catheter CA5a may be forwarded essentially along a straight line through left atrium LA into one of the right pulmonary veins rPVl and rPV2, see essentially straight portion P2d. Distal portion DP5a of catheter CA5a may be anchored or fastened within the respective right pulmonary vein rPVl, rPV2 using balloon Ba5 or another appropriate expandable arrangement. Balloon Ba5 may occlude right pulmonary vein rPVl, rPV2 thereby sealing transport volume TrV at one side or at one input/output location of transport volume TrV.

Catheter CA5a may be a single end -hole catheter having no side holes and may have a variable diameter arrangement (e.g. a balloon or cage) at its distal end DE5a, for instance for fixation and/or for preventing tissue of the left atrium LA to close distal end DE5a. However, other types of tips may be used that are not single end-hole catheters.

Catheter 940b may be inserted as mentioned above for catheter 940. However, distal portion of catheter 940b may be inserted into right pulmonary artery rPA and preferably further into a secondary pulmonary artery but not into left pulmonary artery. In a first embodiment, only one single lumen catheter CA5a is used within one of the right pulmonary veins, e.g. within right pulmonary vein rPVl. The other right pulmonary vein rPV2 does not comprise a catheter. In this case, catheter 940b may be inserted beyond a secondary bifurcation (not illustrated) which is deeper within the pulmonary artery system compared to the primary bifurcation Bil.

Arrows A5a, A5b and A5c illustrate the liquid flow which is established for instance by an external pump (not shown). The external pump may be a membrane pump or another appropriate pump. Transport liquid TrL and/or treatment liquid TL is pumped into catheter 940b, see arrow A5a. Treatment liquid TL is then transported through catheter 940b into transport volume TrV, see arrow A5b and further trough pulmonary arteries to tissue of the alveoli. Thereafter, treatment liquid TL is collected into right pulmonary veins rPV and especially into the first right pulmonary vein rPVl and into distal opening D05a of catheter CA5a. Thereafter, treatment liquid TL is pumped through catheter CA5a and out of a proximal end of catheter CA5a back to the pump of circuitry 500, see arrow A5c.

Furthermore, the pumping direction may be reversed in each application scenario that is mentioned above, i.e. retrograde instead of antegrade. Furthermore, it is possible to switch direction of the fluid flow once or several times.

During treatment of lung L it may be possible that patient P inhales a medicament M or treatment substance in order to promote the treatment by the substance or medicament that flows through the vessels of the lung L and through the tissue of the alveoli. Inhalation may be dedicated to a half 1H, rH of lung L, lobe Lol to Lo5 dedicated or sub-lobe dedicated. Only inhalation of medicament M or other delivery of medicament M through air channels of lung L may be used, i.e. no treatment liquid TL may be used within transport liquid which is transported through transport volume V.

The fluid flow within circuitry 500 may comprise blood as a carrier substance. Alternatively other carrier substances may be used, for instance based on saline and/or on water. According to a further example, a further catheter CA5b is used in addition to catheters CA5a and 940b. The dimensions of catheter CA5b may correspond to catheter CA5a, e.g. same diameter, same length and same way of insertion. However, contrary to catheter CA5a distal portion of catheter CA5b may be arranged within the second right pulmonary vein rPV2. This may enable perfusion of whole right half rH of lung L, for instance if distal portion of catheter 940b is arranged within right pulmonary artery rPA. Alternatively, distal portion of catheter 940b may be arranged deeper within the pulmonary arteries, for instance within third level (tertiary) or fourth level arteries.

Again, the pumping direction may be reversed. Furthermore, it is possible to switch direction of the fluid flow once or several times. Furthermore, optional inhalation (dedicated or not) or other transport (e.g. liquid drops) of medicament M to the right half rH of lung L or to parts thereof through air channels of lung L may be used. Optionally, only medicament M may be inhaled or delivered by liquid drops and treatment liquid TL may not be used within transport volume TrV.

According to a next example, a split tip catheter, see Figure 3 and corresponding description, may be used instead of catheters CA5a and CA5b, with or without inhalation.

As already mentioned above, it is also an option to use the atrial septum AS for catheter(s) CA5a and/or CA5b thereby reaching atrial openings of right pulmonary veins rPVl, rPV2. However, medical reasons and/or the difficulty of realizing small deflecting radii may speak against the route via the atrial septum AS. However, even for the route via the atrial septum AS, the direction of treatment liquid flow may be reversed and/or optional inhalation may be used, e.g. whole lung, half of lung, lobe dedicated or sub-lobe dedicated. Only delivery of medicament M or of treatment liquid TL or both may be used.

Figure 6 illustrates a posterior view of the circuitry 500 of figure 5. However, catheter(s) 940b, CA5b is/are not illustrated. The following steps may be performed in order to insert catheter CA5a into the coronary sinus vein at the outside of heart H.

1.) In this step, a tube PT, e.g. a plastic tube, is inserted intravascular, e.g. through the internal jugular vein IJV and the superior vena cava SVC into heart H. In the region of its distal end, tube PT comprises a bended section, configured such that an opening of tube PT at its distal end faces the opening (coronary sinus ostium 01) to the inner lumen of the coronary sinus vein CSV. Furthermore, tube PT may be used to block the Thebesian valve THV. The distal end of plastic tube PT may be moveable, e.g. with help of a wire. During insertion of tube PT, tube PT may be substantially straight. After insertion, by operating the wire, the distal end can be bended so that the bended section is formed.

2.) Before inserting a guide wire GW, a catheter, for example a puncturing catheter PD (not, illustrated, puncturing device, for instance of company Baylis Medical, details are mentioned below), may be used to form hole HI connecting the inner lumen of coronary sinus vein CSV and the inner lumen of left atrium LA. Catheter PD may be guided inside tube PT, then intravascular along coronary sinus vein CSV to a region of the coronary sinus vein CSV directly opposing the openings of the right pulmonary veins rPVl, rPV2 of left atrium LA. Then, a needle of puncturing catheter PD may be used to puncture hole HI connecting the left atrium LA and the lumen of the coronary sinus vein CSV or an alternating current may be applied to a wire of puncturing catheter PD so that hole HI is burned into the wall of heart H. For example, the diameter of the hole may be 5 French or much less. Accordingly, the diameter of the needle may be 5 French, as well. The Vieussens valve may not be passed thereby, i.e. no additional complications are generated by the Vieussens valve. Thereafter, puncturing catheter PD is pulled back.

3.) Thereafter, a guide wire GW (not illustrated) may be guided through the lumen of tube PT. Guide wire GW may pass the bended region of tube PT, and may be guided into the lumen of coronary sinus vein CSV. Furthermore, guide wire GW may be guided intravascularly along coronary sinus vein CSV and may be inserted from coronary sinus vein CSV into the left atrium LA through hole HI. Thereafter, guide wire GW is forwarded almost or fully along a straight line through left atrium LA into one of right pulmonary veins rPVl, rPV2.

4.) Puncturing tube PT may be removed after a distal portion of guide wire GW is placed within one of the right pulmonary veins rPVl, rPV2, e.g. within rPVl.

5.) Then, an introducer I (not illustrated) may be inserted into the inner lumen of catheter CA5a.

Introducer I may reach from the proximal end to the distal end DE5a. Particularly, introducer I may stretch catheter CA5a so that optional pre-bending or pre-curvature at least partially vanishes. Alternatively, a straight catheter CA5a may be used.

Introducer I may also stretch the diameter variable arrangement, e.g. a cage arrangement so that the diameter variable arrangement as well as the membrane M are in their non-extended states, in which the diameter is smaller, e.g. a factor 10 smaller, than in the extended state. If a balloon Ba5, is used the balloon is hold in its deflated state. Insertion of introducer I into catheter CA5a may be preferably performed outside of body 100, i.e. before first catheter CA5a is inserted into body 100. For insertion, introducer I may be locked or clamped in a fixed position relative to catheter CA5a, e.g. with help of a releasable locking mechanism.

6.) Thereafter, catheter CA5a may be guided along guide wire GW using introducer I, e.g. such that the distal portion DP5a of catheter CA5a moves through superior vena cava SVC, through coronary sinus vein CSV, through left atrium LA up to right pulmonary vein rPV 1 , preferably also into right pulmonary vein rPVl. In this position, balloon Ba5 may be inflated in order to attach catheter CA5a into right pulmonary vein rP V 1.

7.) After step 6, introducer I may be pulled back. Guide wire GW may be pulled back optionally.

Thus, catheter CA5a is ready for lung perfusion as described already in detail above. Catheter CA5a may be pulled back after balloon Ba5 is deflated at the end of perfusion.

Alternatively, a steerable catheter may be used, for instance of the company Merit Medical Systems (may be a registered trade mark). A first guide wire GW1 may be arranged within coronary sinus vein CSV.

The first guide wire GW1 may be used to guide a steerable catheter up to the desired punctuation position. The first guide wire may be retracted. The tip of the steerable catheter may be deflected to the desired punctuation position. An RF wire may be guided through the steerable catheter to the punctuation position. The punctuation may be performed. Thereafter, the RF wire may be used as second guide wire GW2 by forwarding its distal tip into the left atrium and then further to the respective pulmonary vein PV. Alternatively, the RF wire may be retracted and a second guide wire may be introduced through the steerable catheter. The steerable catheter may be forwarded using the RF wire/second guide wire GW. Alternatively, the steerable catheter or a further catheter may be used as an outer catheter in order to guide at least one inner catheter to the left atrium LA and then further to a pulmonary vein.

Puncturing using a separate catheter is optional in this case if the steerable catheter comprises a needle or an RF-wire (radio frequency). If puncturing has to be performed separately before using the steerable catheter, steps 1 and 2 may be performed as mentioned above.

Figure 7 illustrates an upper view of the arrangement 500 (circuitry) of figure 5. However, catheter(s) 940b, CA5b is/are not illustrated. As is also apparent from figure 7, portion P3d of catheter CA5a extents essentially straight through left atrium LA, see portion P3d. Figure 8 illustrates a further embodiment an extra corporeal circular lung perfusion blood flow circuitry 800 for treatment of the right half of the lung or of parts thereof. Circuitry 800 may comprise:

- catheter/cannula CA5a that corresponds to catheter CA5a as described in the description of figures 5 to

7,

- a catheter/cannula CA5b that corresponds essentially to catheter CA5a as described in the description of figures 5 to 7 but its distal portion is arranged within second right pulmonary vein rPV2,

- an outer flexible tube (cannula/catheter) CA5,

- a pump (not illustrated), and

- a device that is similar to device D9.

Catheter/cannula CA5b may have the following portion:

- a first portion Pie that is arranged within right pulmonary vein rPV2 and which may carry an expandable arrangement, e.g. a balloon or a cage,

- a second portion P2e which is arranged within the left atrium and which extends essentially straight through left atrium LA,

- a third portion P3e which is arranged within coronary sinus vein CSV and also within outer flexible tube CA5, and

- a fourth portion P4e extending through right atrium RA, superior vena cava SVC out of body 100 of patient P within outer flexible tube CA5.

Outer flexible tube CA5 may comprise the following portions:

- an optional portion P8A that may extend slightly within left atrium LA, e.g. less than 5 mm (millimeter) or less than 3 mm,

- a portion P8B that extends within coronary sinus vein in the inserted state of outer flexible tube CA5,

- a portion P8C that extends within right atrium RA und within superior vena cava SVC and also out of body 100 of patient, and

- an optional cage arrangement and/or balloon that prevents that outer flexible tube CA5 slides back into coronary sinus vein CSV.

In another embodiment, outer flexible tube CA5 may extend only to opening 01 or partially within coronary sinus vein CSV but not into left atrium LA. This may be advantageous e.g. if coronary sinus vein CSV becomes too narrow near left atrium appendix LAApp, see for instance Figure 5 or 7. If no outer flexible tube CA5 is used, two holes HI a and Hlb may be punctured within coronary sinus vein CSV. Proximal ends of catheters CA5a and CA5b may be connected to the pump (not illustrated) using for instance a three-port connector, e.g. a y-connector or a T-connector. The pump may be connected to the device that is similar to device D9 as is illustrated in principle in Figures 1A and IB and as was described above. However, mentioning of catheters 910a, 910b has been replaced by catheters CA5a and CA5b accordingly.

Again, inhalation may be used optionally or mainly, i.e. it is not necessary to deliver a medicament through pulmonary vessels. Instead inhaled or otherwise through air channels of lung L delivered medicaments M may be removed through transport volume TrV as already explained in detail above.

Perfusion within transport volume TrV may be antegrade if compared with normal liquid flow in pulmonary vessels of lung L, see arrows A5bl, A5b2 and A5c. However, retrograde perfusion is also possible, see arrow A5d

All variants mentioned in this description may comprise or consist of the following method steps which are valid for antegrade perfusion:

1. Isolation

First, an infusion catheter may be inserted for instance into the left internal jugular vein IJV and guided so that the tip of the catheter is within the main pulmonary artery PA (or left (lPA)/right pulmonary artery (rPA), if only one lobe of lung L is treated) to deliver for instance the anticancer drug. Next, the isolation- aspiration catheter (for instance made by the company ReC02hmg) may be inserted for instance into the right internal jugular vein IJV and guided transseptal or via coronary sinus vein CSV into left atrium LA, and into left (lPV)/right pulmonary vein (rPV). At least one occlusion balloon of the isolation-aspiration catheter(s) may be inflated to block the normal venous outflow of blood from the pulmonary vein PV to left atrium LA, thereby isolating lung L or a part of lung L.

2. Infusion

High doses of chemotherapeutic agent or of other medical agent may be delivered directly to lung L or to a part of lung L via the infusion catheter, saturating lung L and the tumor tissue. Alternatively, treatment liquid TL may not be used within transport volume TrV but medicament M may be inhaled/dropped in through the air channel(s) of lung L. In another embodiment treatment liquid TL and medicament M may be used in order to reach synergistic effects.

3. Hemofiltration The isolation-aspiration catheter may collect the blood or other liquid as it exits lung L or a part of lung L into at least one of pulmonary veins PV in the region of the inflated balloon and may then direct it out of the body 100. The blood/liquid may then be passed through a (hemo-)filtration system (for instance a proprietary one made by the company RcCCflung GmbH) and/or an individualized one for patient P, which may reduce the concentration of chemotherapeutic agent or of another medical agent. The filtered blood/liquid may now be returned to the patient's P body 100 through the infusion catheter placed e.g. in internal jugular vein IJV. This may be named as IVLP (in-vivo lung perfusion) or pIVLP™^7® (percutaneous in-vivo lung perfusion).

Alternatively retrograde perfusion may be used as already described in detail above.

Furthermore, the following may apply, especially for a treatment of the lung L:

- Drugs/substances/perfusates for lung L diseases that may be used in all embodiments mentioned above (e.g. half of lung, only lobe dedicated, sub-lobe dedicated) are: Doxorubicin (may be a registered trademark), 5-flurodeoxyuridine (may be a registered trademark), i.e. FUDR (may be a registered trademark), tumor necrosis factor alpha (may be a registered trademark), i.e. TNF-a (may be a registered trademark), paclitaxel (may be a registered trademark), melphalan (may be a registered trademark), gemcitabine (may be a registered trademark), cisplatin (may be a registered trademark). These substances and combinations thereof have all been used for pulmonary metastases. Further substances that may be used separate or in combination with other substances mentioned before are: carboplatin (may be a registered trademark), bleomycin (may be a registered trademark), mitomycin (may be a registered trademark), especially mitomycin C (may be a registered trademark), etc.

- In all embodiments mentioned above, especially for CoV (Corona Virus) diseases Remdesivir (may be a trademark) (Veklury (may be a trademark)) or similar drugs may be used which prevent or inhibit itself or after being converted to an active substance by metabolism viral RNA-Polymerase (RiboNucleic Acid) and prevent reproduction of the virus, preferably through chain termination or through pausing of the polymerase.

- All drugs/substances may be administered also in liposomal-encapsulated, especially gemcitabine, cisplatin and carboplatin. A liposome may be a spherical vesicle comprising or having at least one lipid bilayer.

- pIVLP™/^® (percutaneous in-vivo lung perfusion) or the proposed invention may allow the lung L to be preferentially perfused with high doses of chemotherapy to the tumor, avoiding the dose-limiting effects of systemic toxicity while providing targeted therapy for both macroscopic disease and microscopic disease. - pIVLP™/^® or the proposed invention may be performed with retrograde or antegrade flow. The proposed benefit behind retrograde perfusion is that, by the perfusion through the pulmonary vein PV, collateral veins between the pulmonary and bronchial venous systems may be exploited to deliver drugs to the metastatic lesions. In case of pulmonary embolism the proposed benefit behind retrograde perfusion is that, a retrograde flow and pressure will dissolve and/or flush thrombus even from small capillaries out to pulmonary arteries PA.

- pIVLP™/^® or the proposed invention may be performed even with perfusion pressures lower than 25 mm (millimeter) Hg (mercury column) to avoid producing functional and morphologic damage to the perfused lung L.

- pIVLP™/^® or the proposed invention may be performed with hyperthermic conditions, using enhanced cytotoxic effects at higher temperatures. There may be a combination with the usage of chemical treatment substance (chemotherapy) and/or radiation methods as mentioned above, especially radioactive radiation, etc. Combination may refer to at the same time, i.e. simultaneously, within a period that is less than 24 hours, less than one week or less than one month.

- pIVLP™/^® or the proposed invention may minimize the impact of active drug loss from renal metabolism of the drugs.

- After pIVLP™/^® or the proposed invention is complete, lung L is with varying lengths of washout flushed with flushing fluid, for instance with normothermic saline, Voluven (may be a registered trademark), lactated Ringer’s solution (may be a registered trademark), or Hespan (may be a registered trademark). After complete washout, the pulmonary artery PA and pulmonary vein PV catheters may be removed.

- pIVLP™/^® or the proposed invention may be performed multi times, even as staged procedure over several week, or months, especially advantageous for patients needing repeated therapies.

- pIVLP™/^® or the proposed invention may be performed as bi-lateral or single-lateral or as only partially to a part of an organ that is less than half, less than a third or less than a quarter of the organ.

The treatment fluid (within pulmonary veins PV and/or pulmonary arteries PA and/or within air channels of the lung L) flow may be heated in order to improve the uptake of medicaments/treatment substances by the tissue of the organ and/or by the cells of the organ. If the treatment fluid comprises blood or a high percentage of blood or blood components the heating temperature may be for instance in the range between 39.0 and 44.0 °C (degrees of Celsius), preferably to between 40.0 and 42.5 °C.

However, due to the isolation of transport volume TrV from the body fluid and/or due to the local treatment even higher temperatures may be used, especially if the fluid flow through transport volume TrV does not contain or comprise blood or blood components or only a lower percentage of blood per volume. Therefore, also temperatures above 42.5 °C may be used, for instance above normal blood temperature, above 43 °C, above 44 °C, above 45 °C or even above 50 °C. This may improve the uptake of medicaments/ treatment substances further. However, the temperatures may be below 100 °C (degree Celsius), below 90° C, below 80 °C or below 70° C or below 60°C.

The term “normal body temperature (also known as normothermia or euthermia)”, as used herein, may refer to the typical temperature found in an individual. In humans, the normal body temperature is 37 °C. This value is, however, only an average. The normal body temperature may be slightly higher or lower. A number of factors can influence the body temperature, including age, sex, time of day, and activity level. In babies and children, for example, the average body temperature ranges from 36.6 °C to 37.2 °C. Among adults, the average body temperature ranges from 36.1 °C to 37.2°C. The normal human body temperature range is, thus, typically stated as being between 36.1 °C and 37.5 °C, e.g. 36.1, 36.2, 36.3, 36.4, 36.5, 36.6, 36.7, 36.8, 36.9, 37.0 37.1, 37.2, 37.3, 37.4, or 37.5 °C, in humans.

Furthermore, it is possible to use in all embodiments that are mentioned above an inner surface of the lumen portion and/or inner lumen that comprises a spirally and/or helically surface structure. The spirally and/or helically surface structure may have the effect that the fluid flow within the catheter is rotated as it moves through the catheter. Turbulences may be reduced thereby and/or it may be possible to reach much higher flow rates compared to catheters that have a smooth inner surface, i.e. that do not have spirally and/or helical surface structures on their inner surfaces. However, it is of course possible to use catheters without a spirally and/or helical surface features, if for instance lower flow rates are necessary. The spirally turned flow and/or the rotated flow may prevent clotting of blood cells if the fluid flow comprises blood, especially in slow flow rate conditions. However, there may also be advantages if the fluid flow does not contain blood. The spiral flow may be a laminar spiral flow.

There may be an embodiment in which a single lumen catheter or a dual or multi lumen catheter is used (fixed or non-fixed) wherein the single lumen catheter or the inner catheter of the dual or multi lumen catheter may have a split tip. Each distal tip of the split tip catheter may be associated with or may be carry an expandable arrangement, for instance a balloon or a cage, especially with a cage that carries a membrane. The distal parts of the split tip catheter may be inserted into the left pulmonary veins whereby the right pulmonary veins may be left open. Alternatively, the distal parts of the split tip catheter may be inserted into the right pulmonary veins whereby the left pulmonary veins may be left open.

Furthermore, there may be an embodiment in which a single lumen catheter or a dual catheter is used (fixed or non-fixed) wherein the single lumen catheter or the inner catheter of the dual lumen or multi lumen catheter may have a cage arrangement on its distal end. The cage arrangement may carry a membrane. The membrane may define an opening that faces distally. If the catheter is inserted into the body, the opening of the membrane may face distally in the direction of both right pulmonary veins.

In the following details of a method for puncturing of heart H are provided. However, other methods may be used as well, for instance using a needle. A catheter and/or a wire may be used which has a distal tip which can be heated, for instance using RF (radio frequency) energy, alternating current (ac), direct current (dc) etc. Thus, e.g. a hole may be burned into the septum, e.g. the atrial septum AS or the coronary sinus vein CSV, during puncturing, for instance using temperatures above 100 °C (degrees Celsius) or above 200 °C and less than 1000 °C for instance.

The RF (radio frequency) may be in the range of 100 kHz (kilohertz) to 1 MHz (Megahertz) or in the range of 300 kHz to 600 kHz, for instance around 500 kHz, i.e. in the range of 450 kHz to 550 kHz, e.g. 468 kHz.

The power of the radio frequency energy may have a maximum of 50 W (watt). A power range of 5 W to 100 W may be used, for instance a range of 10 W to 50 W.

A sinus current/voltage may be used for the RF. The sinus current/voltage may be continuous. Alternatively, a pulsed sinus current/voltage may be used for the RF.

All parameters or some of the parameters of the RF equipment may be adjustable by an operator who performs the puncturing, for instance dependent on the specifics of the septum tissue or the coronary sinus vein CSV tissue, e.g. normal septum, fibrotic septum, aneurysmal septum, etc. Preferably, the power may be adjustable.

A solution of Baylis Medical (may be a registered trademark), Montreal, Canada may be used, for instance NRG^® trans-septal needle or Supra Cross^® RF Wire technology. RF generator of type RFP-100A or a further development of this model may be used. This RF generator uses for example a frequency of 468 kHz (kilohertz).

A single puncture of the septum or of coronary sinus vein CSV may be performed from a jugular access or from a femoral access or from another appropriate access using the RF energy. Smaller angles may be possible for the catheter if for instance compared with a needle. Alternatively, the RF method may be used also if two separate punctures are made in the septum. However, usage of needles is possible as well. It is possible to introduce both guide wires first through the atrial septum AS or through the coronary sinus vein CSV. Preferably, separate holes are used for each of the guide wires. Guide wire(s) may be used which include an RF tip. Alternatively, the wire(s) having the RF tip may be pulled back and a further wire may be introduced through the catheter.

Only after both guide wires are in place, both catheters may be introduced using a respective one of the guide wires.

Alternatively, the first puncture may be performed using RF energy or a needle. Thereafter, the first catheter for blood transfer is inserted using the first guide wire. After insertion of the first catheter, the second puncture may be made. A second guide wire or the first guide wire may be used to introduce the second catheter.

Puncturing of the atrial septum or of the coronary sinus vein CSV may be assisted by at least one medical imaging method, preferably by at least two medical imaging methods.

US (ultra-sonic) echo imaging may be used to visualize the movement of heart H and the location of the valves of heart H. No dangerous radiation may result from ultra-sonic imaging. An ultra-sonic transmitter may be introduced for instance via the esophagus, e.g. trans-esophagus echo (TEE) may be used.

X-ray radiation preferably in combination with fluorescence (fluoroscopy), may be used in order to visualize the location of catheters (comprising for instance at least one X-ray marker, or the devices are usually radiopaque) and/or the location of guide wire(s), snares etc.

Thus, transseptal puncturing or puncturing of other tissue (e.g. of coronary sinus vein CSV) may be guided by TEE and by fluoroscopy or by other imaging methods. At least two different image generating methods may be used.

Furthermore, the puncturing technique may be combined with a steerable catheter. Plenty of these catheters are available on the market, especially for the coronary sinus vein CSV, see for instance catheters of Merit Medical Systems (may be a registered trademark). In all embodiments mentioned above, it is also possible to use a soft guide wire and a stiffer guide wire which does not bend so easy if compared with the soft guide wire. The following steps may be performed, preferably in combination with snaring:

1) Introduce a soft guide wire.

2) Introduce catheter using the soft wire as a guide.

3) Optionally, remove soft wire, for instance by pulling back the soft wire out of the catheter.

4) Introduce stiffer guide wire into the catheter, e.g. there may be a change of wire from soft wire to the stiffer wire.

The catheter may be removed, e.g. pulled back. Thereafter, the stiffer wire may be used to introduce a catheter or catheters.

With other words, the following is described:

A) Antegrade flow through at least one left lobe/parts of a left lobe:

- The catheter/cannula occludes and inject/pump in the distal left pulmonary artery 1PA when the balloon is inflated.

- The catheter/cannula occludes and vents the left pulmonary vein/s 1PV when the balloon is inflated.“

B) Antegrade flow through at least one right lobe/parts of a right lobe:

- The catheter/cannula occludes and inject/pump in the distal right pulmonary artery rPA when the balloon is inflated.

- The catheter/cannula occludes and vents the right pulmonary vein/s rPV when the balloon is inflated.“

C) Retrograde flow through at least one left lobe/parts of a left lobe:

- The catheter/catheter occludes and inject/pump in the left pulmonary vein/s 1PV when the balloon is inflated.

- The catheter/cannula occludes and vents the left pulmonary artery 1PA when the balloon is inflated.

D) Retrograde flow through at least one right lobe/parts of a right lobe:

- The catheter/cannula occludes and inject/pump in the right pulmonary vein/s rPV when the balloon is inflated.

- The catheter/cannula occludes and vents the right pulmonary artery rPA when the balloon is inflated.

Thus, a closed perfusion circuit of at least one lobe Lo4, Lo5 of left half of lung L or of at least one lobe Lol to Lo3 of right half rH lung L is provided. Stepwise treatment of left/right or parts of left/right lobe Lol to Lo5 of lung L are possible as well, e.g. although only parts of lung L are treated at each time the whole lung L may be treated step by step thereby enabling patient P to breath with his own currently untreated parts of lung L. Thus, heart H and/or lung L support, e.g. using a heart lung machine, may not be necessary but may, however, be an option.

Instead of recirculation, it is of course possible to use single-pass fluid transport in all embodiments mentioned above, e.g. half of lung, only lobe dedicated, sub-lobe dedicated.

It is of course possible to use only one catheter/cannula (end portion) within the respective pair of pulmonary veins, e.g. within the two right pulmonary veins rPV or within the left pulmonary veins 1PV.

As far as outer catheters are mentioned (e.g. in coronary sinus vein CSV or through atrial septum AS) in this application, it is possible to use a cage arrangement or an inflatable arrangement on its distal dip in order to provide a fixation at the wall of the left atrium LA.

The present inventor found that isolated and/or located lung perfusion allows the lung to be preferentially perfused with doses of a medicament avoiding side effects the administration of the medicament to other parts of the body, e.g. organs and/or tissues, of a patient might have. In this way, lung diseases can be treated.

Thus, a next aspect of the invention relates to a perfusate comprising, consisting essentially of, or consisting of a medicament for use in the local treatment of a lung disease (in a patient), wherein the local treatment is restricted/limited to the lung (of the patient). The treatment may be an in vivo (within the living organism), ex vivo (out of the living organisms), or in vitro (outside of the normal biological context) treatment of the lung. Thus, the lung comprised in a patient may be treated. Alternatively, the lung may be explanted and subsequently treated. After the treatment, the lung may be re-implanted into the patient or into another patient.

It is preferred that the local treatment is restricted to a part of the lung. In one embodiment, the local treatment is restricted to the left half of the lung or right half of the lung, particularly to a dedicated lobe of the left half of the lung or to a dedicated lobe of the right half of the lung, more particularly to a dedicated sub-lobe of the left half of the lung or to a dedicated sub-lobe of the right half of the lung.

It is preferred that the perfusate comprising the medicament is to be administered intravascular. In this case, the medicament is to be administered via (a) blood vessel(s). Specifically, the administration is to be carried out intravascular and percutaneous. In this respect, percutaneous administration refers to a medical procedure where access to the lung or lung tissue is done via needle-puncture of the skin, rather than by using an “open” approach where the lung or lung tissue is exposed (typically with the use of a scalpel).

The percutaneous approach is commonly used in vascular procedures.

For example, the intravascular or intravascular and percutaneous administration is to be conducted through an endovascularly inserted cannula or catheter, preferably a cannula or catheter according to the aspect described above. The catheter or cannula may have a length of at least 90 cm (centimeter) or of at least 1 m (meter), especially a portion which is configured to be arranged within the body of the patient.

In one preferred embodiment, the perfusate comprising the medicament is to be administered antegrade. The antegrade administration may be through the pulmonary artery, specifically through the right ventricle of the heart. Preferably, the administration is through the left pulmonary artery or right pulmonary artery. More preferably, the administration is through the ventricular opening of the pulmonary artery PA at least beyond the first bifurcations Bil of the pulmonary artery PA into the right pulmonary artery rPA. Even more preferably, the administration is through the ventricular opening of the pulmonary artery PA at least beyond the first bifurcation Bil and further at least beyond one of the secondary bifurcations Bi2, preferably into a tertiary artery 1PA1, 1PA2, rPAl, rPA2 of the pulmonary arteries.

In one alternative preferred embodiment, the perfusate comprising the medicament is to be administered retrograde. The retrograde administration is preferably:

- through at least one left pulmonary vein 1PV, more preferably through two or both left pulmonary veins lPVs, and/or

- through at least one right pulmonary vein rPV, more preferably through two or both right pulmonary veins rPVs, and/or specifically trough the left atrium of the heart and more specifically through at least one of atrial septum (AS) and coronary sinus vein (CSV).

In one embodiment, the perfusate is an aqueous solution. In one preferred embodiment, the aqueous solution is blood or a salt solution. In case of blood, the blood preferably corresponds to the blood group of the patient to whom the blood is to be administered. In case of a salt solution, the salt solution is preferably a physiological salt solution. In one preferred embodiment, the lung disease is selected from the group consisting of an Acute respiratory distress symptom (ARDS), a Chronic obstructive pulmonary disease (COPD), Pulmonary embolism (PE), Pulmonary hypertension (PHT), lung fibrosis, pneumonia, lung cancer, and an infection.

Specifically, the infection is a viral or bacterial infection. More specifically, the virus infection is an infection caused by a virus of the family of Coronaviridae, Arteriviridae, Roniviridae, or Mesoniviridae . Even more specifically, the virus of the family of Coronaviridae is selected from the group consisting of MERS-CoV, SARS-CoV, SARS-CoV-2 and mutations thereof, and an Infectious Bronchitis Virus (IBV).

Specifically, the infection is a viral or bacterial infection. More specifically, the virus infection is an infection caused by a virus of the family of Coronaviridae, Arteriviridae, Roniviridae, or Mesoniviridae. Even more specifically, the virus of the family of Coronaviridae is selected from the group consisting of MERS-CoV and mutations thereof, SARS-CoV and mutations thereof, SARS-CoV-2 and mutations thereof, and an Infectious Bronchitis Virus (IBV).

In one more preferred embodiment, the medicament is selected from the group consisting of a chemotherapeutic agent, an antiviral agent, an antibiotic, an anti-inflammatory agent, an immunomodulatory agent, an antibody, an anti-cytokinergic agent, a barrier-protective agent, a steroid, and stem cells (stem cell therapy), or is a combination thereof.

In one even more preferred embodiment, the chemotherapeutic agent is selected from the group consisting of alkylating agents, anthracyclines, cytoskeletal disruptors (taxanes), epothilones, histone deacetylase inhibitors, inhibitors of topoisomerase I, inhibitors of topoisomerase II, kinase inhibitors, nucleotide analogs and precursor analogs, peptide antibiotics, platinium-based agents, retinoids and vinca alkaloids and its derivatives, or is a combination thereof. Especially, the chemotherapeutic agent is selected from the group consisting of paclitaxel, doxorubicin, liposomal-encapsulated doxorubicin (liporubicin), 5-flurodeoxyuridine (FUDR), tumor necrosis factor alpha (TNF-a), melphalan, gemcitabine, carboplatin, cisplatin, bleomycin, imatinib, and smitomycin, or is a combination thereof.

Especially, the anti-inflammatory agent is dexamethasone.

Targeted high-dose administration of barrier-protective agents in diseases with acute endothelial or epithelial barrier loss (COVID-19, ARDS), e.g. angiotensin-(l-7) or sphingosine-1 -phosphate, is of advantage as these agents are not very suitable for systemic application due to their strong vasoactive effects.

The local therapy of chronic lung diseases as described above is advantageous with drugs which usually have high systemic side effects (e.g. imatinib for reverse-remodeling in pulmonary hypertension).

The medicament as described above is preferably to be administered at a flow rate of between 0.25 l/min to 8 l/min, preferably 0.5 l/min to 3.5 l/min, more preferably 1 l/min to 1.5 l/min, e.g. 0.25, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5 or 8

1/m in.

The medicament is preferably to be administered at a concentration/amount which is lower than the concentration/amount usually used, e.g. for intravenous administration. The present inventor surprisingly found that due to the local/isolated treatment of the lung, in particular part of the lung, no diluting effects occur. In addition, no medicament loss from renal metabolism occur. In this way, the exposure of the body to the medicament can be reduced. In addition, the treatment costs can be reduced.

The medicament is preferably to be administered at a concentration/amount which is higher than the concentration/amount usually used, e.g. for intravenous administration. The present inventor surprisingly found that due to the local/isolated treatment of the lung, in particular part of the lung, dose-limiting effects of systemic toxicity can be avoided. In addition, less or even no side effects occur due to the local/isolated treatment of the lung, in particular part of the lung. In this way, a safe and reproducible treatment can be ensured. In other words, the local treatment has the advantage that high-doses of the medicament can be administered to the lung, in particular part of the lung, while the exposure to sensitive critical organs can be limited. In this way, severe complications, like systemic side effects and toxicity associated with higher doses, can be avoided. The concentration/amount may be raised by at least 20 percent, e.g. of the dose per square meter body surface of the patient, by at least 50 percent or even by at least 100 percent. One possible upper limit is an increase by at least factor 10 or even by factor 100 or by at least factor 1000 or even more. The reference may be the recommended concentration/amount for intravenous application of the medicament without local restriction, e.g. application to the whole body.

For example, the medicament doxorubicin can be administered at a dose between 40 mg/m² and 80 mg/m², the tumor necrosis factor alpha (TNF-a) can be administered at a dose between 30 mg/m² and 50 mg/m², e.g. at 45 mg/m², and/or cisplatin can be administered at a dose between 70 mg/m² and 200 mg/m² to treat lung cancer. The reference area may be the body surface of the patient, e.g. body surface area BSA.

A further advantage of the above described local treatment of the lung disease is that the patient receiving the therapy is mobile and not necessarily bedridden.

An additional advantage of the above described local treatment of the lung disease is that access to the lung, specifically part of the lung, is done via needle-puncture of the skin, rather than by using an “open” approach where the lung or lung tissue is exposed (typically with the use of a scalpel). Thus, the above described local/isolated treatment of the lung, in particular part of the lung, in order to treat a lung disease allows an efficient treatment of the lung or of a part of the lung. The duration of treatment of one portion of the lung may be in the range of 5 minutes to 60 minutes or in the range of 10 minutes to 40 minutes. Thereafter, another portion or the same portion may be treated, e.g. after a short break within the range of 5 minutes to 30 minutes. Thus, it is for instance possible to treat one half or another portion of the lung first, then the other half or another portion and optionally repeate this cycle at least one time or at least two times.

The cannulas may be within the body for an appropriate duration in the range of 20 minutes to 24 hours or in the range of 1 hour to 20 hours or in the range of 2 hours to 10 hours. Accordingly, the patient can receive a treatment without open chest surgery (thoracotomy) which mitigates the negative collateral side effects of thoracotomy considerably, e.g. minimizing risks of infection, bleeding, etc.

A next aspect of the invention relates to a combination comprising, consisting essentially of, or consisting of:

- a perfusate comprising, consisting essentially of, or consisting of a medicament, and

- an inhalant or fluid comprising, consisting essentially of, or consisting of a medicament for use in the local treatment of a lung disease, wherein the local treatment is restricted to the lung.

The medicament as part of the inhalant or fluid is administered via the upper respiratory tract and reaches the lung in this way.

The perfusate is preferably a perfusate according to the aspect described above. The inhalant preferably comprises the medicament in a gaseous and/or nebulized form. The inhalant may have the form of a liquid nebula.

In this way, the treatment of the lung disease can be further improved.

Although embodiments of the present disclosure and their advantages have been described in detail, it should be understood that various changes, substitutions and alterations may be made therein without departing from the spirit and scope of the disclosure as defined by the appended claims. For example, it will be readily understood by those skilled in the art that many of the features, functions, processes and methods described herein may be varied while remaining within the scope of the present disclosure. Moreover, the scope of the present application is not intended to be limited to the particular embodiments of the system, process, manufacture, method or steps described in the present disclosure. As one of ordinary skill in the art will readily appreciate from the disclosure of the present disclosure systems, processes, manufacture, methods or steps presently existing or to be developed later that perform substantially the same function or achieve substantially the same result as the corresponding embodiments described herein may be utilized according to the present disclosure. Accordingly, the appended claims are intended to include within their scope such systems, processes, methods or steps. The embodiments mentioned in the first part of the description may be combined with each other. The embodiments of the description of figures may also be combined with each other. Further, it is possible to combine embodiments mentioned in the first part of the description with examples of the second part of the description which relates to figures 1 to 8.

Claims

1. Catheter or cannula (910a, 910b, CA5a, CA5b) for treating the lung (L) of a patient (P), comprising: a lumen portion (LP1 to LP5) comprising a proximal end (PE) and a distal end (DE), a proximal opening (PO) at the proximal end (PE), a distal opening (DO) at the distal end (DE), wherein an inner lumen (LI 7) of the lumen portion (LP1 to LP5) extends from the proximal opening (PO) to the distal opening (DO), wherein the lumen portion (LP1 to LP5) comprises a first portion (PI a to Pie) and a second portion (P2a to P2e), wherein the second portion (P2a to P2e) is arranged proximally to the first portion (PI a to Pie), and wherein the catheter or cannula (910a, 910b, CA5a, CA5b) is configured such that, when inserted as intended, the first portion (Pla to Pie) is located in and extends into a pulmonary vein (PV) of the patient (P) and the second portion (P2a to P2e) is located in and extends through the left atrium (LA) of the heart (H) of the patient (P).

2. Catheter or cannula (CA5a, CA5b) according to claim 1, wherein the lumen portion (LP5) comprises a third portion (P3d) that is arranged proximally of the second portion (P2d), the catheter or cannula (CA5a, CA5b) is configured such that, when inserted as intended, the third portion (P3d) is located in and extends along the coronary sinus vein (CSV) of the heart (H) and through a hole (HI) within the wall of the coronary sinus vein (CSV) and within a wall of the left atrium (LA), and wherein the pulmonary vein (PV) is one of the right pulmonary veins (rPVl, rPV2).

3. Catheter or cannula (CA5a) according to claim 2, wherein the lumen portion (LP5) comprises a fourth portion (P4d) that is arranged proximally of the third portion (P3d), the catheter or cannula (CA5a) is configured such that, when inserted as intended, the fourth portion (P4d) is located in and extends through the right atrium (RA) of the heart (H) and through the superior vena cava (SVC) of the patient (P).

4. Catheter or cannula (CA5a) according to claim 3, wherein the length of the catheter or cannula (CA5a) is in the range of 50 cm to 90 cm or in the range of 50 cm to 110 cm, and wherein the maximum outer diameter of the catheter or cannula (CA5a) at the first portion (Pld) or the maximum outer diameter of the catheter or cannula (CA5a) is in the range of 5 French to 16 French or of 5 French to 19 French or in the range of 9 French to 11 French.

5. Catheter or cannula (CA5a) according to claim 2, wherein the lumen portion (LP5) comprises a fourth portion (P4d) that is arranged proximally of the third portion (P3d), the catheter or cannula (CA5a) is configured such that, when inserted as intended, the fourth portion (P4d) is located in and extends through the inferior vena cava (IVC) of the patient (P).

6. Catheter or cannula (CA5a) according to claim 5, wherein the length of the catheter or cannula (CA5a) is in the range of 70 cm to 110 cm or in the range of 70 cm to 130 cm, and wherein the maximum outer diameter of the catheter or cannula (CA5a) at the first portion (PI a) or the maximum outer diameter of the catheter or cannula (CA5a), is in the range of 5 French to 16 French or of 5 French to 19 French or in the range of 9 French to 11 French.

7. Catheter or cannula (910a, 910b) according to claim 1, wherein the lumen portion (LP1, LP2) comprises a third portion (P3a, P3b) that is arranged proximally of the second portion (P2a, P2b), the catheter or cannula (910a, 910b) is configured such that, when inserted as intended, the third portion (P3a, P3b) is located in and extends through the atrial septum (AS) of the heart (H), and wherein the pulmonary vein (PV) is one of the left pulmonary veins (IPV4, 1PV2) or wherein the pulmonary vein (PV) is one of the right pulmonary veins (rPVl, rPV2).

8. Catheter or cannula (910a, 910b) according to claim 7, wherein the lumen portion (LP1, LP2) comprises a fourth portion (P4a, P4b) that is arranged proximally of the third portion (P3a, P3b), the catheter or cannula (910a, 910b) is configured such that, when inserted as intended, the fourth portion (P4a, P4b) is located in and extends through the right atrium (RA) of the heart (H) and through the superior vena cava (SVC) of the patient (P).

9. Catheter or cannula (910a, 910b) according to claim 8, wherein the length of the catheter or cannula (910a, 910b) is in the range of 50 cm to 90 cm or in the range of 50 cm to 110 cm, and wherein the maximum outer diameter of the catheter or cannula (910a, 910b) at the first portion (PI a, Plb) or the maximum outer diameter of the catheter or cannula (910a, 910b), is in the range of 5 French to 16 French or of 5 French to 19 French or in the range of 9 French to 11 French.

10. Catheter or cannula (910a, 910b) according to claim 7, wherein the lumen portion (LP1, LP2) comprises a fourth portion (P4a, P4b) that is arranged proximally of the third portion (P3a, P3b), the catheter or cannula (910a, 910b) is configured such that, when inserted as intended, the fourth portion (P4a, P4b) is located in and extends along the inferior vena cava (IVC) of the patient (P).

11. Catheter or cannula (910a, 910b) according to claim 10, wherein the length of the catheter or cannula is in the range of 70 cm to 110 cm or in the range of 70 cm to 130 cm, and wherein the maximum outer diameter of the catheter or cannula (910a, 910b) at the first portion (PI a, Plb) or the maximum outer diameter of the catheter or cannula (910a, 910b), is in the range of 5 French to 16 French or of 5 French to 19 French or in the range of 9 French to 11 French.

12. Catheter or cannula (910a, 910b, CA5a) according to any one of the previous claims, wherein the first portion (Pla to Pie) carries a radially expandable arrangement that has an expanded state and a non-expanded state, wherein the radially expandable arrangement is an inflatable balloon (Bal, Ba2, Ba5), and wherein the catheter or cannula (910a, 910b, CA5a) comprises at least one further lumen (CHI, CH2) that is coupled to the inflatable balloon (Bal, Ba2, Ba5), preferably in order to guide an auxiliary liquid to the balloon (Bal, Ba2, Ba5) and from the balloon (Bal, Ba2, Ba5).

13. Catheter or cannula (940, 940b) for treating the lung (L) or another organ of a patient (P), especially pulmonary artery catheter or cannula, comprising: a lumen portion (LP3) comprising a proximal end (PE) and a distal end (DE), a proximal opening (PO) at the proximal end (PE), a distal opening (DO) at the distal end (DE), wherein an inner lumen (L17) of the lumen portion (LP3) extends from the proximal opening (PO) to the distal opening (DO), the lumen portion (LP3) comprising a first portion (Pic, Pie) and a second portion (P2c, P2e), wherein the second portion (P2c, P2e) is arranged proximally of the first portion (Pic, Pie), and wherein the catheter or cannula (940, 940b) is configured such that, when inserted as intended, the first portion (Pic, Pie) is located in a secondary pulmonary artery (1PA, rPA) of the patient (P) or in a tertiary pulmonary artery (1PA1, 1PA2, rPAl, rPA2) of the patient (P) and the second portion (P2c, P2e) is located in a primary pulmonary artery (PA) of the patient (P).

14. Catheter or cannula (940, 940b) according to claim 13, wherein the lumen portion (LP3) comprises a third portion (P3c, P3e) that is arranged proximally of the second portion (P2c, P2e), the catheter or cannula (940, 940b) is configured such that, when inserted as intended, the third portion (P3c, P3e) is located in and extends through the right ventricle (RV) of the heart (H).

15. Catheter or cannula (940, 940b) according to claim 14, wherein the lumen portion (LP3) comprises a fourth portion (P4c, P4e) that is arranged proximally of the third portion (P3c, P3e), the catheter or cannula (940, 940b) is configured such that, when inserted as intended, the fourth portion (P4c, P4e) is located in and extends along the right atrium (RA) of the heart (H) and through the superior vena cava (SVC) of the patient (P).

16. Catheter or cannula (940, 940b) according to claim 15, wherein the length of the catheter or cannula is in the range of 60 cm to 90 cm or in the range of 90 cm to 130 cm, and wherein the maximum outer diameter of the catheter or cannula (940) at the first portion or the maximum outer diameter of the catheter or cannula (940, 940b), is in the range of 5 French to 22 French or of 8 French to 22 French or in the range of 9 French to 22 French.

17. Catheter or cannula (940, 940b) according to claim 14, wherein the lumen portion (LP) comprises a fourth portion (P4c, P4e) that is arranged proximally of the third portion (P3c, P4e), the catheter or cannula (940, 940b) is configured such that, when inserted as intended, the fourth portion (P4c, P4e) is located in and extends through the inferior vena cava (IVC) of the patient (P).

18. Catheter or cannula (940, 940b) according to claim 17, wherein the length of the catheter or cannula is in the range of 90 cm to 120 cm or in the range of 120 cm to 160 cm, and wherein the maximum outer diameter of the catheter or cannula (940, 940b, 940c) at the first portion or the maximum outer diameter of the catheter or cannula (940, 940b), is in the range of 5 French to 22 French or of 8 French to 22 French or in the range of 9 French to 22 French.

19. Catheter or cannula (940, 940b, 940c) according to any one of the claims 13 to 18, wherein the first portion (Pla to Pie) carries a radially expandable arrangement that has an expanded state and a non-expanded state, wherein the radially expandable arrangement is an inflatable balloon (Bal), and wherein the catheter or cannula (940, 940b) comprises at least one further lumen (CHI, CH2) that is coupled to the inflatable balloon (Bal), preferably in order to guide an auxiliary liquid to the balloon (Bal) and from the balloon (Bal).

20. Set of catheter or cannulas (910a, 910b, CA5a, 940, 940b), comprising: at least one of a pulmonary vein catheter or cannula (910a, 910b, CA5a) according to any one of the claims 1 to 12, and at least one pulmonary artery catheter or cannula (940, 940b) according to any one of the claims 13 to 19, and preferably at least one pump.

21. Set of catheters or cannulas (910a, 910b, CA5, 940) according to claim 20, comprising a left pulmonary vein catheter or cannula (910a, 910b) according to any one of the claims 7 to 11, a right pulmonary vein catheter or cannula (CA5a, CA5b) according to any one of the claims 2 to 6, and at least one pulmonary artery catheter or cannula (940, 940b, 940c) according to one of the claims 13 to 19.

22. Method for treating the lung (L) or another organ of a patient (P), comprising: guiding a distal portion (DP2a, DP2b, DP5a) of a catheter or cannula (910a, 910b, CA5) up to the left atrium (LA) of the heart (H) of the patient (P), forwarding the distal portion (DP2a, DP2b, DP5a) of the catheter or cannula (910a, 910b, CA5) through the left atrium (LA) at least up to at least one of the atrial openings of the pulmonary veins (1PV, rPV) within the left atrium (LA), and perfusing at least one of a treatment liquid (TL) for treating the lung (L) of a patient (P) and a transport liquid (TrL) through the catheter or cannula (910a, 910b, CA5a, CA5b).

23. Method according to claim 22, wherein the catheter or cannula (910a, 910b, CA5a, CA5b) is a single lumen catheter or cannula having only one distal portion (DP2a, DP2b, DP5a).

24. Method according to claim 22 or 23, comprising, inserting the distal portion (DP5a) of the catheter or cannula (CA5a) into the coronary sinus vein (CSV), guiding the distal portion (DP5a) of the catheter or cannula (CA5a) through the coronary sinus vein (CSV), and inserting the distal portion (DP5a) from the coronary sinus vein (CSV) into the left atrium (LA) of the heart (H), forwarding the distal portion (DP5a) through the left atrium (LA) at least up to at least one of the atrial openings of the right pulmonary veins (rPV).

25. Method according to claim 24, comprising: puncturing a hole (HI) into the wall of the coronary sinus vein (CSV) and through the wall of the left atrium (LA), preferably before inserting the distal portion (DP5a) of the catheter or cannula (CA5a) into the coronary sinus vein (CSV).

26. Method according to claim 25, wherein the punctured hole (HI) is arranged near the left atrium appendix (LAApp), especially within a distance of less than 2 cm to an inner wall of the left atrium appendix (LAApp) or of less than 1 cm to an inner wall of the left atrium appendix (LAApp).

27. Method according to any one of the claims 24 to 26, wherein only one right pulmonary vein (rPVl, rPV2) is used for perfusion.

28. Method according to any one of the claims 24 to 26, wherein a distal portion of a second catheter or cannula (CA5b) is guided through the coronary sinus vein (CSV) into the other right pulmonary vein (rPV2), and wherein preferably an outer flexible tube (CA5) is used to guide the second catheter or cannula (CA5b).

29. Method according to any one of the claims 24 to 26, wherein the catheter or cannula (CA5a) is a split tip catheter or cannula (CA3), wherein a first tip (LI 8 a) of the split tip catheter or cannula (CA3) is arranged within a first right pulmonary vein (rPVl) and a second tip (L18b) is arranged within a second right pulmonary vein (rPV2).

30. Method according to any one of the claims 24 to 29, wherein the distal portion (DP5a) of the catheter or cannula (CA5a, CA5b, CA3) carries an inflatable balloon (Ba5).

31. Method according to any one of the claims 24 to 30, comprising: guiding a distal portion (DP lb) of a pulmonary artery catheter or cannula (940b) up to the left ventricle (LV) of the heart (H) of the patient (P), forwarding the distal portion (DP lb) of the pulmonary artery catheter or cannula (940b) through the ventricular opening of the pulmonary artery (PA) at least beyond the first bifurcations (Bil) of the pulmonary artery (PA) into the right pulmonary artery (rPA), and perfusing the at least one of the treatment liquid (TL) for treating the lung (L) of a patient (P) or of the transport liquid (TrL) through the pulmonary artery catheter or cannula (940).

32. Method according to claim 31, comprising: forwarding the distal portion (DP lb) of the pulmonary artery catheter or cannula (940b) through the ventricular opening of the pulmonary artery (PA) at least beyond the first bifurcation (Bil) and further at least beyond one of the secondary bifurcations (Bi2) into a tertiary artery (1PA1, 1PA2, rPAl, rPA2) of the pulmonary arteries.

33. Method according to claim 22 or 23, comprising: puncturing a hole into the atrial septum (AS), and inserting a distal portion (DP2a, DP2b) of the catheter or cannula (910a, 910b) through the hole in the atrial septum (AS).

34. Method according to claim 34, wherein only one left pulmonary vein (IPV4, 1PV2) is used for perfusion.

35. Method according to claim 34, wherein a distal portion of a second catheter or cannula (910b) is guided through the atrial septum (AS) into the other left pulmonary vein (1PV2), and wherein preferably an outer flexible tube is used to guide the second catheter or cannula.

36. Method according to claim 34, wherein the catheter or cannula (910a, 910b) is a split tip catheter or cannula (CA3), and wherein a first tip (LI 8 a) of the split tip catheter or cannula (CA3) is arranged within a first left pulmonary vein (IPV4) and a second tip (L18b) is arranged within a second left pulmonary vein (1PV2).

37. Method according to any one of the claims 33 to 36, wherein the distal portion (DP2a, DP2b) of the catheter or cannula (910a, 910b, CA3) carries an inflatable balloon (Bal, Ba2).

38. Method according to any one of the claims 33 to 37, comprising: guiding a distal portion (DP lb) of a pulmonary artery catheter or cannula (940) up to the left ventricle (LV) of the heart (H) of the patient (P), forwarding the distal portion (DP lb) through the ventricular opening of the pulmonary artery (PA) at least beyond the first bifurcation (Bil) of the pulmonary artery (PA) into the left pulmonary artery (1PA), perfusing the at least one of the treatment liquid (TL) for treating the lung (L) of a patient (P) or of the transport liquid (TrL) through the pulmonary artery catheter or cannula (940).

39. Method according to claim 38, comprising: forwarding the distal portion (DP lb) through the ventricular opening of the pulmonary artery (PA) at least beyond the first bifurcation (Bil) and further at least beyond one of the secondary bifurcations (Bi2) into a tertiary artery (1PA1, 1PA2, rPAl, rPA2) of the pulmonary arteries.

40. Method according to any one of the claims 22 to 32 and according to any one of the claims 33 to 37.

41. Method according to any one of the claims 22 to 40, comprising: arranging at least one substance transport channel (Tu) within at least one air transport channel of the lung (L), and applying a treatment substance (M) through the at least one substance transport channel (Tu) into a dedicated region of the lung (L) simultaneously to the perfusing of the at least one of the treatment liquid (TL) for treating the lung (L) of a patient (P) and the transport liquid (TrL) through the catheter or cannula (910a, 910b, CA5a).

42. Method according to claim 41, wherein the treatment substance (M) comprises stem cells of at least one kind of tissue in the lung (L) or a medicament against lung (L) cancer or a medicament against a lung (L) infection.

43. Method according any one of the claims 22 to 42, wherein a catheter or cannula according to any one of the claims 1 to 10 or a catheter or cannula set according to claim 20 or 21 is used.

44. Catheter or cannula (910a, 910b, CA5, 940, 940b) according to any one of the claims 1 to 21, configured to be used or used in a method according to any one of the claims 22 to 42.

45. A perfusate comprising a medicament for use in the local treatment of a lung disease (in a patient), wherein the local treatment is restricted to the lung (of the patient).

46. The perfusate for use of claim 45, wherein the local treatment is restricted to a part of the lung.

47. The perfusate for use of claim 46, wherein the local treatment is restricted to the left half of the lung or right half of the lung.

48. The perfuse for use of claim 47, wherein the local treatment is restricted to a dedicated lobe of the left half of the lung or to a dedicated lobe of the right half of the lung.

49. The perfusate for use of claim 48, wherein the local treatment is restricted to a dedicated sub-lobe of the left half of the lung or to a dedicated sub-lobe of the right half of the lung.

50. The perfusate for use of any one of claims 45 to 50, wherein the perfusate comprising the medicament is to be administered intravascular.

51. The perfusate for use of claim 50, wherein the perfusate comprising the medicament is to be administered intravascular and percutaneous.

52. The perfusate for use of claims 50 or 51, wherein the intravascular or intravascular and percutaneous administration is to be conducted through an endovascularly inserted cannula or catheter, preferably a cannula or catheter according to any one of claims 1 to 19.

53. The perfusate for use of any one of claims 45 to 52, wherein the perfusate comprising the medicament is to be administered antegrade.

54. The perfusate for use of claim 53, wherein the antegrade administration is through the pulmonary artery, preferably through the right ventricle of the heart.

55. The perfusate for use of claim 54, wherein the administration is through the left pulmonary artery or right pulmonary artery.

56. The perfusate for use of claim 55, wherein the administration is through the ventricular opening of the pulmonary artery (PA) at least beyond the first bifurcations (Bil ) of the pulmonary artery (PA) into the right pulmonary artery (rPA).

57. The perfusate for use of claim 56, wherein the administration is through the ventricular opening of the pulmonary artery (PA) at least beyond the first bifurcation (Bil) and further at least beyond one of the secondary bifurcations (Bi2), preferably into a tertiary artery (1PA1, 1PA2, rPAl, rPA2) of the pulmonary arteries.

58. The perfusate for use of claims 45 to 52, wherein the perfusate comprising the medicament is to be administered retrograde.

59. The perfusate for use of claim 58, wherein the retrograde administration is through at least one left pulmonary vein (1PV), preferably two left pulmonary veins (lPVs), and/or at least one right pulmonary vein (rPV), preferably two right pulmonary veins (rPVs), preferably trough the left atrium of the heart and more preferably through at least one of atrial septum (AS) and coronary sinus vein (CSV).

60. The perfusate for use of any one of claims 45 to 59, wherein the perfusate is an aqueous solution, preferably blood or a salt solution.

61. The perfusate for use of claim 60, wherein the blood corresponds to the blood group of the patient to whom the blood is to be administered.

62. The perfusate for use of claim 60, wherein the salt solution is physiological salt solution.

63. The perfusate for use of any one of claims 45 to 62, wherein the lung disease is selected from the group consisting of an Acute respiratory distress symptom (ARDS), a Chronic obstructive pulmonary disease (COPD), Pulmonary embolism (PE), Pulmonary hypertension (PHT), lung fibrosis, pneumonia, lung cancer, and an infection.

64. The perfusate for use of claim 63, wherein the infection is a viral or bacterial infection.

65. The perfusate for use of claim 64, wherein the virus infection is an infection caused by a virus of the family of Coronaviridae, Arteriviridae, Roniviridae, or Mesoniviridae .

66. The perfusate for use of claim 65, wherein the virus of the family of Coronaviridae is selected from the group consisting of MERS-CoV, SARS-CoV, SARS-CoV-2, and an Infectious Bronchitis Virus (IBV).

67. The perfusate for use of any one of claims 45 to 66, wherein the medicament is selected from the group consisting of a medicament for the treatment of a Chronic obstructive pulmonary disease (COPD), a medicament for the treatment of an Acute respiratory distress symptom (ARDS), a medicament for the treatment of Pulmonary embolism (PE), a medicament for the treatment of Pulmonary hypertension (PHT), a medicament for the treatment of lung fibrosis, a medicament for the treatment of pneumonia, and a medicament for the treatment of lung cancer, and a medicament for the treatment of an infection.

68. The perfusate for use of claim 67, wherein the infection is a viral or bacterial infection.

69. The perfusate for use of claim 68, wherein the virus infection is an infection caused by a virus of the family of Coronaviridae, Arteriviridae, Roniviridae, or Mesoniviridae.

70. The perfusate for use of claim 69, wherein the virus of the family of Coronaviridae is selected from the group consisting of MERS-CoV, SARS-CoV, SARS-CoV-2, and an Infectious Bronchitis Virus (IBV).

71. The perfusate for use of any one of claims 45 to 70, wherein the medicament is selected from the group consisting of a chemotherapeutic agent, an antiviral agent, an antibiotic, an anti-inflammatory agent, an immunomodulatory agent, an antibody, an anti-cytokinergic agent, a barrier-protective agent, a steroid, and stem cells (stem cell therapy), or is a combination thereof.

72. The perfusate for use of claim 71, wherein the chemotherapeutic agent is selected from the group consisting of alkylating agents, anthracy clines, cytoskeletal disruptors (taxanes), epothilones, histone deacetylase inhibitors, inhibitors of topoisomerase I, inhibitors of topoisomerase II, kinase inhibitors, nucleotide analogs and precursor analogs, peptide antibiotics, platinium -based agents, retinoids and vinca alkaloids and its derivatives, or is a combination thereof.

73. The perfusate for use of claims 71 or 72, wherein the chemotherapeutic agent is selected from the group consisting of paclitaxel, doxorubicin, liposomal-encapsulated doxorubicin (liporubicin), 5- flurodeoxyuridine (FUDR), tumor necrosis factor alpha (TNF-a), melphalan, gemcitabine, carboplatin, cisplatin, bleomycin, imatinib, and smitomycin, or is a combination thereof.

74. The perfusate for use of any one of claims 71 to 73, wherein the antiviral agent is selected from the group consisting of chloroquine, remdesivir, darunavir, favipiravir, lopinavir, and ritonavir, or is a combination thereof.

75. The perfusate for use of any one of claims 45 to 74, wherein the medicament is to be administered at a flow rate of between 0.25 1/min to 8 1/min, preferably 0.5 1/min to 3.5 1/min, more preferably 1 1/min to 1.5 1/min, and even more preferably 1.25 1/min.

76. A combination comprising, consisting essentially of, or consisting of a perfusate comprising a medicament and an inhalant or fluid comprising a medicament for use in the local treatment of a lung disease, wherein the local treatment is restricted to the lung.