RU2437165C1 - Method of immune corrector therapy of myocardial infraction in rats - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: modelling a myocardial infraction is followed by intravenous introduction of the immune corrector tamerite 3 mg/kg in an animal every days for seven days. The histological results of the myocardial tissue presented after the first, third and seventh days show the sufficiency and efficacy of the therapy.

EFFECT: effective therapy of the acute myocardial infraction ensured by reducing the intensity of an acute inflammatory reaction, providing faster granulation tissue formation.

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Description

The invention relates to experimental medicine, namely to an experimental form of myocardial infarction in rats, and can be used after modeling myocardial infarction in rats for subsequent drug exposure and observation of its effectiveness.

Myocardial infarction is one of the most frequent nosological forms and makes up 3.9% among men and 2.2% among women, which brings it to one of the first places in the world. Moreover, in Russia 330 men and 154 women per 100 thousand people die from myocardial infarction every year, which is 3.2 times more than in the United States. These circumstances indicate the high relevance of the problem of MI, in particular its treatment.

In the Recommendations of the European Cardiology Society working group (2000) and the Russian Recommendations based on them (2001), the treatment of developed myocardial infarction is based on the use of beta-blockers, nitrates, calcium antagonists and antiplatelet agents (aspirin, thienopyridines, blockers of glycoprotein IIb / IIIa platelet receptors ) Despite the large number of different surgical and conservative methods of treatment, mortality in acute myocardial infarction continues to be high: early complications lead to 10-15% of hospital mortality.

The main causes of death are the development of heart failure and disturbances in rhythm and conduction, due primarily to the magnitude of the developed myocardial infarction and the progressive involvement of intact myocardial cells in the process. High mortality dictates the need to develop new methods of treatment for this serious disease that would prevent the development or reduce the severity of these complications of myocardial infarction.

Modeling of acute myocardial infarction in rats, according to the authors, is the most justified, because these laboratory animals have a course of physiological and pathological processes similar to humans, which allows using the results of animal studies to create new methods of treating this disease in humans.

Atenolol is known for the treatment of myocardial infarction, which has a complex mechanism of action: it blocks beta-1-adrenergic receptors, due to which the stimulating effect on the heart of sympathetic innervation and the circulation of catecholamines in the blood, has antianginal, hypotensive and antiarrhythmic effects.

Introduction: initial administration is carried out intravenously at a dose of 5 mg, after 5 minutes another 5 mg, then after an hour, the drug is taken orally at 50-100 mg per day.

Disadvantage: the drug is contraindicated in bronchial obstructive syndrome, sinus node weakness syndrome, AV block and congestive heart failure; reliable efficacy in the reduction of recurrent myocardial infarction and a decrease in mortality is manifested only with prolonged treatment (about 2 years).

Information sources

1. Selected sections of internal medicine. Yekaterinburg, 2007. Volume 4, pp. 101-172.

2. Medicines in Russia: a Handbook. M .: AstraFarmService, 2003, p. 3-1104.

Known drug acetylsalicylic acid, which is included in international and Russian recommendations for the treatment of myocardial infarction - a prototype.

Acetylsalicylic acid inhibits the activity of COX - the main enzyme of the metabolism of arachidonic acid, which is a precursor of prostaglandins, which provides anti-inflammatory, analgesic and antipyretic effects, and also inhibits the formation of TXA2, thereby inhibiting platelet aggregation.

Its positive aspects: with prolonged use (at least 2 years), it reduces the frequency of repeated myocardial infarction.

Negative sides: the drug is contraindicated in peptic ulcers, local bleeding, hemorrhagic diathesis; 40% of patients do not show an anti-aggregation effect, which is considered the main element of the anti-infarction action of the drug.

Information sources

3. Selected sections of internal medicine. Yekaterinburg, 2007. Volume 4, pp. 101-172.

4. Drugs in Russia: a Handbook. M .: AstraFarmService, 2003, p. 3-1104.

An object of the invention is to increase the effectiveness of the treatment of myocardial infarction with the use of different chemical structures of drugs with immunocorrection properties.

To solve this problem, a method is proposed for treating myocardial infarction immunocorrector in rats after its modeling, based on medical intervention, characterized in that after creating a myocardial infarction model, the tamerite immunocorrector is administered intravenously at a dose of 3 mg / kg every day for seven days with histological studies of myocardial tissue after the first, third and seventh days, and the results of these studies judge the sufficiency and effectiveness of the treatment Niya.

A group of drugs is known that belong to the class of immunocorrector derivatives of different chemical groups, for example, tamerite. The action of these substances differs from the drugs currently used in medical practice. To date, the effect of ischemic and acute phases of myocardial infarction has not been studied. This application describes the clinical trials of these drugs for the treatment of experimental myocardial infarction in rats. The effect of other immunizers is being studied.

The treatment is as follows.

Simulation of myocardial infarction in rats of the same severity is performed, followed by intravenous administration of the tamerite compound to one group of animals, while the study of indicators of the cytolytic syndrome - transaminases and histological examination of myocardial tissue is carried out for 7 days.

Acting on the nature of the island-inflammatory reaction (by decreasing the intake of neutrophilic white blood cells that release inflammation stimulating factors, tamerite in a dosage of 3 mg / kg corrects the course of the acute phase of the systemic inflammatory response syndrome, which leads to a decrease in the severity of the leukocyte reaction, stimulates the migration of immunocompetent cells - lymphocytes, plasma cells, mast cells, macrophages in the foci of necrosis, accelerates the formation of granulation tissue with the proliferation of fibroblast cells and causes substitution necrosis scar tissue provided active fibroblasts and fibrous structures, without phenomena of purulent inflammation of scar tissue.

The effect on the course of the acute phase of experimental myocardial infarction tamerite in 50 cases was monitored.

The results of the experiments.

Comparison of the effect of tamerite immunocorrector on biochemical blood parameters (M ± m) in the dynamics of the development of experimental myocardial infarction Indicators Intact rats Animals with experimental myocardial infarction 1st day IM 5th day 7th day tamerite tamerite tamerite (n = 5) (n = 5) (n = 5) (n = 5) CPK (μmol / L-min) 146.92 ± 22.6 323 ± 43.79 * 405 ± 27.84 * 291.35 ± 18.90 * ACT (μmol / L-day) 0.193 ± 0.014 0.254 ± 0.034 0.204 ± 0.029 0.177 ± 0.024 ^x LDH _1-2 (μmol / L-day) 165.15 ± 34.6 248.84 ± 41.10 * 187.94 ± 34.37 Note. The significance of differences in biochemical parameters in experimental and intact animals: * - p <0.05, in animals treated with tamerite ^x - p <0.05

Comparison of histomorphological data at various times of experimental myocardial infarction during treatment with immunocorrector tamerite Study Dates MI in intact animals MI in animals treated with tamerite 1st day 1. The damage zone is transmural in nature, represented by cardiomyocytes with the phenomena of karyolysis, plasmolysis and plasmorexis. 1. The damage zone is subepicardial in nature, represented by cardiomyocytes with the phenomena of karyolysis, plasmolysis and plasmorexis. 2. Infiltration of the damage zone by diffuse segmented white blood cells. 2. Migration of polymorphic nuclear leukocytes was not detected. The demarcation shaft is not formed. 5th day 1. The infarction zone is represented by necrotic cardiomyocytes, surrounded by a demarcation shaft. 1. The heart attack zone is represented by necrotic altered cardiomyocytes with the phenomena of plasmolysis, plasmorexis and karyolysis. 2. There are signs of granulation tissue formation. 2. On the periphery of the perifocal region, accumulations of lymphocytes and macrophages are detected, fibroblast proliferation is noted, that is, elements of granulation tissue. 3. Neutrophilic infiltration of endomysium is noted in adjacent structures. 7th day 1. The disintegration of muscle cells persists. 1. The infarct zone is represented by granulation tissue from proliferating fibroblasts and macrophages. 2. At the edges of the necrosis zone, granulation tissue is formed with a large number of fibroblasts, sinusoidal hemocapillaries. 2. In the scar area, moderate lymphocytic infiltration, macrophages and proliferating fibroblasts are determined. 3. Infiltration by lymphocytes and segmented leukocytes remains.

The fundamental difference between the histomorphological picture in animals with experimental myocardial infarction, receiving immunocorrectors of various chemical structures and not receiving treatment, was revealed in the presence of untreated animals with marked leukocyte inflammation in the infarction zone, which led to an increase in the spread of inflammation to the initially intact myocardium and much later myocardial scarring. In animals with experimental myocardial infarction receiving immunocorrectors, for example, tamerite, the drug caused a predominance of a lyphocyte-macrophage inflammatory reaction, accelerating regenerative processes both in the necrosis zone and in near-infarction areas. Moreover, almost the same treatment effectiveness and, most importantly, the same histomorphological picture in the inflammation zone allow us to conclude that immunocorrectors with different chemical structures have the same mechanism of action and have the same effective therapeutic effect in case of myocardial infarction.

Claims (1)

A method of treating myocardial infarction immunocorrector in rats after its modeling, based on drug intervention, and after creating a myocardial infarction model, the tamerite immunocorrector is administered intravenously at a dose of 3 mg / kg every day for seven days with histological examination of myocardial tissue after the first, third and the seventh day, and the results of these studies judge the sufficiency and effectiveness of the treatment.