RU2266125C1 - Method for treating acute myocardial infarction at st segment lifting - Google Patents

Abstract

FIELD: medicine, cardiology.

SUBSTANCE: one should introduce the suspension of autologous mononuclear medullary cells without preliminary cultivation in to the mouth of coronary artery nourishing infarction area. Cell suspension should be introduced at the quantity of 100-150 mln. cells immediately after stenting coronary artery due to technique of passive passage. The procedure should be performed on the 14^th - 21^st d against the onset of the disease mentioned. The method provides efficient counterbalance of cardiomyocytes due to applying valuable stem cells at excluding complications induced by arterial occlusion.

EFFECT: higher efficiency of therapy.

1 ex, 1 tbl

Description

The invention relates to medicine, specifically to cardiology, and relates to methods for treating acute myocardial infarction with ST segment elevation.

It has been established that existing methods of emergency myocardial revascularization (thrombolysis, emergency balloon angioplasty) have exhausted their potential in limiting the size of myocardial necrosis [1]. At the same time, myocardial infarction takes the first place among the causes of the development of chronic heart failure, and the magnitude of myocardial necrosis is directly related to its frequency and severity [2]. In this regard, the urgent problem is the development of methods for the treatment of myocardial infarction, providing replenishment of the lost number of cardiomyocytes.

There is a method of treating patients with acute myocardial infarction with ST segment elevation [3], when a suspension of autologous mononuclear bone marrow cells, which are pre-cultured for 24 hours with autologous blood plasma, is injected into a heart attack-related coronary artery on the 7th day from the onset of the disease during time of repeated coronary angiography, the introduction of cell suspension is carried out during occlusion of the lumen of the coronary artery.

This method is the closest to the claimed technical essence and the achieved result and is selected as a prototype.

The disadvantage of this method is the need to perform coronary angiography twice and occlusion of the coronary artery during the introduction of cell suspension, which may increase the risk of complications of interventions, cultivation of autologous mononuclear bone marrow cells with autologous blood plasma during the day, as well as the early introduction of cells from the onset of the disease .

The purpose of the invention is to increase the effectiveness of treatment and reduce the risk of complications by eliminating repeated interventions, as well as eliminating additional effects on bone marrow mononuclear cells.

The goal is achieved by a technical solution, which is a method of treating acute myocardial infarction with ST segment elevation, which consists in introducing a suspension of autologous mononuclear bone marrow cells without prior cultivation in the coronary artery feeding the myocardial infarction region. Cell suspension is administered in an amount of 100-150 million cells immediately after stenting of the coronary artery. There is no need to create occlusion of the coronary artery during the introduction of cell suspension. The procedure is carried out on the 14th-21st days from the onset of the disease. Bone marrow aspiration is carried out from the iliac crest after puncture of its anteroposterior spine. Autologous mononuclear bone marrow cells are isolated by gradient centrifugation.

New in the proposed method is the introduction of cell suspension in the amount of 100-150 million cells without prior cultivation at the mouth of the affected coronary artery by passive passage immediately after stenting the site of narrowing of the coronary artery without creating occlusion in it during the introduction of cell suspension on the 14th 21 days from the onset of the disease.

Bone marrow mononuclear cells are very plastic material, so it is advisable to exclude additional effects on them, which will preserve their natural ability to secrete various bioactive substances and morphogenetic properties, which in turn will manifest itself in a more powerful induction of reparative processes in the damaged myocardium and will lead to increased efficiency treatment.

In the pathogenesis of acute myocardial infarction, an inflammatory reaction to the resulting myocardial necrosis occupies an important place. The transfer of bone marrow mononuclear cells in the early stages of the disease (up to 14 days of myocardial infarction), when an inflammatory reaction continues in the heart tissue, may not lead to the desired result, since transferred bone marrow mononuclear cells may be more involved in the inflammatory response cascade rather than in the formation of new vessels and functioning cardiomyocytes.

An important circumstance is that most cardiologists are limited in the ability to perform emergency primary balloon angioplasty and stenting of the coronary artery, and therefore, thrombolytic therapy is performed for myocardial reperfusion. Coronary angiography and stenting of the affected artery is performed only in the subacute stage (14th-21st day of the disease) of myocardial infarction. At the same time, a full-fledged scar tissue with new vessels is not yet in time to form, in addition, an increased content of adhesion molecules remains in the affected myocardium [4], which ensures fixation (adhesion) of transferred bone marrow mononuclear cells in the myocardium. That is why we proposed a method of free passage of cell suspension with selective introduction of a heart-attached coronary artery at the mouth. The free passage of cell suspension eliminates the damaging effects of the dilated balloon on the wall of the coronary artery and reduces the risk of thrombosis. The introduction of cell suspension is performed immediately after stenting of the coronary artery, which saves the patient from the need for a double interventional intervention, which significantly reduces the risk of possible complications both during and after the procedure, which generally increases the effectiveness of treatment.

The method is as follows: on the 14th-21st days of acute myocardial infarction under local anesthesia with a 10% solution of lidocaine, the iliac crest is punctured in the anteroposterior spine, 100-120 ml of bone marrow are aspirated into two 60-ml syringes with 5 ml of heparin, mononuclear bone marrow cells are isolated by gradient centrifugation. A suspension of bone marrow mononuclear cells with a concentration of from 2 to 5 × 10 ⁶ cells is prepared. Coronary angiography is performed and the affected artery is stented, then a catheter is placed at the mouth of the affected coronary artery and a slow suspension of bone marrow mononuclear cells is performed.

Example. Patient G., 59 years old, was admitted to the emergency cardiology department 3 hours after the onset of anginal status with signs of ischemic myocardial damage in the anterolateral wall of the left ventricle and acute heart failure II FC according to T. Killip. The patient underwent systemic thrombolytic therapy with cabicinase 750,000 units effective by indirect signs of myocardial reperfusion 5 hours after the onset of the disease. According to loading perfusion myocardial scintigraphy with thallium 199, a stable 45% and transient 15% myocardial perfusion defects are detected. In addition, establish a decrease in the ejection fraction of the left ventricle to 50%. On the 16th day of the disease, under local anesthesia with a 10% solution of lidocaine, the iliac crest is punctured in the anterosuperior spine, 100 ml of bone marrow are aspirated, autologous mononuclear bone marrow cells are isolated by gradient centrifugation, coronary angiography is performed, and the affected coronary artery is stented with optimal as a result, the mouth of the affected coronary artery is catheterized, a suspension of bone marrow mononuclear cells in the amount of 90 million cells is introduced by passive passage. The patient tolerates all these interventions well, no complications have been recorded. Before administration, autologous mononuclear bone marrow cells are labeled with 99 Te - NMRAO radiopharmaceutical (Ceretec ^tmo ). It is revealed that 30 minutes after the introduction of cell suspension in the myocardium, about 2.5% of the cells are visualized, after 3 hours 1.8%, after 24 hours 1.6% of the cells. After treatment, the patient is monitored for 6 months and positive results of treatment are observed, which is manifested by the absence of an increase in left ventricular volumes (end-diastolic volume 123 versus 102 ml, end-systolic volume 51 versus 40 ml) by an increase in the ejection fraction of the left ventricle by 10%, a decrease in the size of a stable perfusion defect by 8% (45% against 37%). No clinical signs of chronic heart failure were detected during the observation period.

The proposed method for the treatment of acute myocardial infarction with ST segment elevation was used in 12 patients (Table 1).

Table 1
The main data of clinical and instrumental examination Indicators Before treatment After 6 months of treatment R Age years 57.7 ± 9.4 Reperfusion time 5.2 ± 1.4 BWW, ml 124.7 ± 26.7 140.5 ± 46.5 NS CSR, ml 74.7 ± 22.5 69.5 ± 28.4 NS PV,% 40.7 ± 10.7 51.5 ± 4.5 0,07 Stable perfusion defect,% 33 ± 12.5 21.2 ± 13.9 0.04 Transient perfusion defect,% 15.5 ± 11.6 18 ± 4.8 NS The accumulation percentage of 99 m of technetril 24 after administration 2% NS - no differences, BWW - end-diastolic volume of the left ventricle, CSR - end-systolic volume of the left ventricle, EF - ejection fraction of the left ventricle.

As can be seen from the table, the proposed method of treatment allowed for the delivery of autologous mononuclear bone marrow cells to the myocardium, to achieve a decrease in the severity of postinfarction remodeling of the left ventricle, to improve its contractile function and myocardial perfusion.

The method proposed by the authors allows to increase the effectiveness of treatment of patients with acute myocardial infarction with ST segment elevation and reduce the number of complications of interventions.

List of references

1. Topol E.J. Current status and future prospects for acute myocardial infarction therapy. Circulation 2003; 108 (suppl III): III-6-III-13.

2. Braunwald E. Myocardial reperfusion, limitation of infarct size, reduction of left ventricular dysfunction, and improved survival. Should the paradigm be expanded. Circulation. - 1989. - Vol. 79, N2. - 441-444.

3. Strauer B.E., Brehm M., Zeus T., et al. Repair of infarcted myocardium by autologous intracoronary mononuclkear bone marrow cell transplantation in humans. Circulation 2002; 106: 1913-1918.

4. Xie Y, Zhou T., Shen W., et al. Soluble cell adhesion molecules in patients with acute coronary syndrome. Clin Med J. 2000: 113: 286-288.

Claims (1)

A method for the treatment of acute myocardial infarction with ST segment elevation, which consists in delivering autologous mononuclear bone marrow cells obtained by gradient centrifugation to the myocardial necrosis zone by introducing them into the coronary artery feeding the region of myocardial infarction, characterized in that the cell suspension without prior cultivation in 100-150 million cells are injected into the mouth of the affected coronary artery by passive passage immediately after stenting the site of narrowing of the coronary artery without creating occlusion in it during the introduction of the cell suspension on the 14-21 th days of the onset of the disease.