RU2634375C2 - Method for preventing postinfarction cardiac remodeling in experiment - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: method comprises dressing the upper third of the left coronary artery and administering the Alloplant biopreparation into the stenosed artery circulation. The administration is carried out by intramyocardial injection of 3.0 mg of a biopreparation diluted in physiological saline. Injections are performed immediately after stenosing the artery at 6 points, by 0.5 mg each.

EFFECT: effective stimulation of endogenous mechanisms of myocardial regeneration, preventing postinfarction cardiac remodeling.

2 tbl, 1 ex

Description

The invention relates to the field of experimental medicine.

At present, it has been proved that with all the perfection of the existing methods of treatment, myocardial infarction, developing as a result of a coronary catastrophe, is inevitably accompanied by necrosis of the part of the heart muscle that has fallen into the area of ischemic damage. The organization of the focus of necrosis is accompanied by the replacement of dead cardiomyocytes with connective tissue. The result of this is the formation of either a scar or aneurysm. The irreversible loss of part of the cardiomyocytes increases the functional load on the intact myocardium, which triggers the process of its hypertrophy. All this leads to remodeling of the heart, a violation of its function and intracardiac hemodynamics.

A known method of preventing heart remodeling after myocardial infarction using drugs that are inhibitors of angiotensin converting enzyme (ACE) [1; 2].

This method is the closest to the claimed and selected as a prototype.

The disadvantages of this method are: the need for prolonged use of ACE inhibitors, the presence of a number of contraindications for ACE inhibitors [3; four]. This circumstance, to a large extent, determines the high risk of developing adverse remodeling of the heart in people who have had myocardial infarction.

Thus, the development of new methods for preventing post-infarction remodeling of the heart is very relevant.

The objective of the invention is to develop a method that allows the experimental conditions to effectively prevent the development of post-infarction remodeling of the heart, stimulating the endogenous mechanisms of myocardial regeneration.

The problem is solved by performing immediately after stenosis of the upper third of the left coronary artery intramyocardial injection of Alloplant biologic in the stenosed artery pool. A dispersed form of the Alloplant biological product is used, which is diluted in physiological saline and administered at a dose of 3.0 mg intramyocardially. Spend 6 injections of 0.5 mg each.

It is known that Alloplant is an allogeneic biological product and is produced by the All-Russian Center for Ophthalmic and Plastic Surgery, Ministry of Health of Russia, Ufa. This biological product is used for plastic and regenerative surgery [5].

The inventors first experimentally showed that immediately after stenosis of the coronary artery, a single application of the dispersed Alloplant form in the form of 6 intramyocardial injections of 0.5 mg each into the stenotic coronary artery pool prevents the connective tissue degeneration of the myocardium, the development of aneurysm and impaired intracardiac hemodynamics. The process of healing (regeneration) of muscle tissue in the area of necrotic lesion in the natural mode and when using Alloplant is carried out by different endogenous mechanisms. Their combination can prevent the process of post-infarction remodeling of the heart.

New in the proposed method is the introduction of Alloplant into the pool of the coronary artery immediately after its stenosis in a dose of 3.0 mg in the form of intramyocardial injections of 0.5 mg each.

No information was found in the patent and medical literature that the use of Alloplant in animals with experimental myocardial infarction (stenosis of the coronary artery) can prevent the development of aneurysm, impaired intracardiac hemodynamics and heart hypertrophy. This property Alloplant does not follow from the prior art in this field and is not obvious to a specialist. The proposed method can be used to create biomedical technologies that prevent the development of postinfarction remodeling of the heart.

Based on the foregoing, it should be considered that the proposed invention meets the conditions of patentability: “Novelty”, “Inventive step”, “Industrial applicability”.

The invention will be clear from the following description.

The experiments were performed on male Wistar rats weighing 200-250 g. Post-infarction remodeling of the heart was induced by stenosis of the upper third of the left descending coronary artery [6]. Immediately after arterial stenosis, 6 intramyocardial injections of a 0.5 mg each dispersed Alloplant form dissolved in physiological saline were performed. After which the animals were kept under standard vivarium conditions. The severity of the process of post-infarction remodeling of the heart was evaluated using magnetic resonance imaging (MRI) performed on 7, 14 and 45 days after the intervention (stenosis of the left descending coronary artery).

Example. The study of the ability of Alloplant in the experiment to prevent post-infarction remodeling of the heart was carried out according to the following scheme. 12 Wistar rats were taken and 2 groups of animals were formed:

Group I (n = 6) served as a control. Animals of this group underwent stenosis of the coronary artery. Group II (n = 6) was the main one. Together with stenosis of the coronary artery, animals of this group underwent 6 intramyocardial injections of the Alloplant biological product, 0.5 mg each. Prior to the study, all animals underwent cardiac MRI. Repeated MRI examinations of the heart were performed on the 7th, 14th and 45th days after the interventions. After this period, animals of groups I and II, using raush anesthesia, were withdrawn from the experiment. The hearts of animals were dissected and subjected to morphometry [7, 8]. The data obtained were processed using the non-parametric Mann-Whitney test.

According to the results of an MRI examination of the heart of animals in the control group, after stenosis of the coronary artery, by the 7th day there were obvious signs of post-infarction remodeling. At a later date, these changes only intensified. The appearance and increase in the volume of the damaged myocardium, as well as an increase in BWW, indicating progressive post-infarction remodeling of the heart, were noted (Table 1). In the main group on day 7, changes similar to the control group were observed. However, in subsequent periods, there was no gain in changes indicating the development of post-infarction heart remodeling. At the same time, by the 45th day, the control and the main groups significantly differed in all considered parameters. The results of morphometric examinations of the heart (table 2) also showed that in the control group the percentage of animals with morpholigically visible heart attack and aneurysm of the left ventricle was significantly higher. Animals of this group were characterized by a high index value - heart weight / body weight. For the heart of rats of the main group, these changes were uncharacteristic or significantly less pronounced.

This result suggests that a single myocardial injection of Alloplant simultaneously with modeling of an experimental heart attack creates conditions for stimulating regenerative processes in the myocardium and preventing post-infarction heart remodeling.

The invention can be used in experimental studies to create new biomedical technologies for preventing post-infarction heart remodeling.

Literature

1. Preobrazhensky D.V., Sidorenko B.A., Batyraliev T.A. et al. Use of angiotensin-converting enzyme inhibitors in patients after acute myocardial infarction // Cardiology. - 2008. - No. 11. - S. 64-68.

2. Guide to cardiology: Textbook in 3 t. / Ed. G.I. Storozhakova, A.A. Gorbachenkova. - 2008. - T. 1. - 672 p.

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5. Muldashev E.R., Muslimov S.A., Vyalkov V.A. et al. Alloplant biomaterial for regenerative surgery // Patent for invention. RU 2189257.

6. Afanasyev S.A., Rebrova T.Yu., Kondratyev D.S. Features of the phospholipid composition of erythrocyte membranes in conditions of post-infarction cardiosclerosis // Biomedical chemistry. - 2007. - T. 53, No. 5. - S. 541-546.

7. Usacheva M.A., Popkova E.V., Smirnova E.A. et al. Adaptation of the cardiovascular system to postinfarction cardiosclerosis in rats with different congenital myocardial adrenoreactivity // Bull. expert. biol. - 2007. - T. 144, No. 12. - S. 624-628.

8. Satoh N, Sato T, Shimada M. et al Lusitropic effect of MCC-135 is associated with improvement of sarcoplasmic reticulum function in ventricular muscles of rats with diabetic cardiomyopathy // J. Pharmacol. Exp. Ther. - 2001. - V. 298, No. 3. - P. l161-1166.

Claims (1)

A method of preventing post-infarction remodeling of the heart in an experiment, characterized in that immediately after stenosis of the upper third of the left descending coronary artery, a dispersed form of Alloplant is administered at 6 points in its pool, the drug is administered once by intramyocardial injection of 0.5 mg each, before use Alloplant is diluted in physiological saline.