Method of treating experimental myocardial infraction in rats

FIELD: medicine.

SUBSTANCE: modelling a myocardial infraction is followed in a rat is followed by intravenous introduction of the immune corrector tamerite 3 mg/kg. The preparation is injected daily 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 with high possibility of cure ensured by reduced manifestations of systemic inflammation response syndrome, faster granulation tissue formation and necrotic zone replacement by cicatricial tissue.

 

The invention relates to experimental medicine for the treatment of experimental myocardial infarction in rats by medical intervention to monitor the effectiveness of the latter.

Myocardial infarction is one of the most frequent forms of diseases and is 3.9% among males and 2.2% among women, which puts it on one of the first places in the world. In Russia from myocardial infarction die 330 men and 154 women per 100 thousand population, which is 3.2 times more than in the US. These circumstances indicate a high relevance of the problem to THEM, in particular his treatment.

The Recommendations of the working group of the European society of Cardiology (2000) and based on them the Russian Recommendations (2001), the treatment of the developed myocardial infarction is based on the use of beta-blockers, nitrates, calcium antagonists and antiplatelet agents (aspirin, thienopyridine, antagonists of glycoprotein IIb/IIIa receptors on platelets). 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 is heart failure and arrhythmias and conduction, subject to the first value of developing myocardial infarction and progressive involvement in the process of intact cells of the myocardium. High mortality dictates the need to develop new treatments for this debilitating disease that would prevent the development or reduced the severity of these complications of myocardial infarction.

Modeling of acute myocardial infarction in rats, in our opinion, is the most reasonable, because these laboratory animals are similar to humans during physiological and pathological processes, which allows to use the results of animal studies to develop new methods of treatment of this disease in humans.

Known for the treatment of myocardial infarction drug atenolol, which has a complex mechanism of action: blocks beta-1-adrenergic receptors, which decreases the stimulating effect on the heart sympathetic innervation and circulating in the blood catecholamines, has antianginal, hypotensive and antiarrhythmic effect.

Introduction: a basic introduction is given intravenously in a dose of 5 mg, after 5 minutes, another 5 mg, then after an hour it starts taking the drug inside of 50-100 mg per day.

Disadvantage: the drug is contraindicated in bronchial obstructive syndrome, syndrome, sick sinus, AV-blockade and congestive heart failure; reliable performance in ischemia of repeated heart attacks and reducing mortality prospect who is only in long-term care (about 2 years).

Source:

1. "Selected topics in internal medicine", Ekaterinburg, 2007. Volume 4, p.101-172.

2. Drugs in Russia: a Handbook. M: Attraversare, 2003, p.3-1104. Str-188.

Known drug acetylsalicylic acid, which is included in international and national recommendations for the treatment of myocardial infarction PROTOTYPE.

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

Its positive side: with long-term use (at least 2 years) reduces the frequency of repeated heart attacks.

Negative sides: the drug is contraindicated in peptic ulcers, local bleeding, hemorrhagic diathesis; 40% of patients do not manifest antiaggregatory effect, considered to be the basic element protivoinfektsionnogo of action of the drug.

Source:

3. "Selected topics in internal medicine", Ekaterinburg, 2007. Volume 4, p.101-172.

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

An object of the invention is to increase the effectiveness of treatment of myocardial infarction more what ereatest cure.

To solve this problem is proposed a method of treatment of experimental myocardial infarction in rats after simulation-based medical intervention, characterized in that after creating a model of myocardial infarction perform intravenous immunocorrector Tamarit in the dosage 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 are judged on the adequacy and effectiveness of the treatment.

The treatment is as follows.

Is intravenous connection tamerica after creating a model of myocardial infarction with subsequent study of indicators of cytolytic syndrome - transaminase and histological examination of tissue infarction within 7 days.

Drug Tamarit belongs to the class of immunomodulators. The action of these substances differs from that currently used in medical practice drugs.

Influencing the nature of the acute inflammatory reaction (reducing intake of neutrophilic leukocytes that produce factors that stimulate inflammation Tamarit in the dosage of 3 mg/kg corrects for the acute phase of the syndrome of systemic inflammatory response, which leads to a decrease in the expression of the leukocyte is nuclear biological chemical (NBC reactions stimulates migration immunocompetent cells - lymphocytes, plasma cells, mast cells, macrophages in the necrotic foci, accelerates the formation of granulation tissue with proliferation of fibroblastic cells number and calls the substitution necrosis scar tissue, represented by the active fibroblasts and fibrous structures, without the effects of purulent inflammation of scar tissue.

Traced the action of tamerica during acute phase of experimental myocardial infarction in 50 cases.

The experimental results.

On the first day of myocardial infarction without the introduction of the drug was observed pronounced dystrophic reaction with stromal edema, loss of transverse and longitudinal iscertainly myofibrils, and in the future - grained and glycated decay.

Areas adjacent to the area of infarction, were subject to significant changes and expressed partial atrophy of myocardiocytes and structural changes similar to those in the zone of necrosis, until dystrophic and necrobiotic changes in individual muscle fibers and their groups, lokalizovalsya in the wall of the left ventricle Area of the heart (in most cases transmural) was represented by cardiomyocytes events karyolysis, plasmolysis and plasmolysis. Showed moderate diffuse infiltration, Prime is asih structures observed phenomena edema, the plethora of vessels, Indonesia with the formation of the sludge systems.

On the first day of myocardial infarction with drug Area of infarction localized subepicardial on the lateral wall of the left and right ventricles. Presents necrotic modified cardiomyocytes with the phenomena of plasmolysis and plasmolysis. In the border zone vessels diperkirakan. Migration of polymorphonuclear leukocytes was not found. Demarcation shaft is not formed. Saved infarction remains moderate swelling.

On the fifth day of myocardial infarction without injection area of infarction was defined as mainly transmural. The necrotic cardiomyocytes were surrounded demarcation shaft, showed signs of formation of granulation tissue, fibroblasts appear, emocapella. In adjacent structures were detected distribution of infiltration on Indonesia

On the fifth day of myocardial infarction with drug Area of infarction presents a deathly modified cardiomyocytes with the phenomena of plasmolysis, plasmolysis and karyolysis. Infarction zone defined sanguineous capillaries sinusoidal type. On the periphery of the perifocal region detected accumulations of lymphocytes and macrophages. There is a proliferation of fibroblasts, i.e. elements of granulation the Noah fabric. In areas adjacent to the infarction area in the myocardium remains moderate edema and plethora of vessels Indonesia. Polymorphonuclear leukocytes in the demarcation lines are not defined. On the lateral wall of the right ventricle cardiomyocytes is not damaged, but the vessels Indonesia full-blooded, gleams them expanded.

On the seventh day of myocardial infarction without injection area of necrosis in the wall of the left ventricle in 100% of cases were characterized as transmural. Histological signs of stage (formation of granulation tissue at the edges of the zone of necrosis with a large number of fibroblasts and macrophages, sinusoidal emocapella, substitute the affected area) when the continuing disintegration of muscle cells and the continuing infiltration of the myocardium by lymphocyte and segmented by leukocytes. In some cases the vessels was determined by the boundary distance of cells with signs of leukodepleted.

On the seventh day of myocardial infarction with drug area of infarction localized subepicardial on the lateral wall of the left ventricle. Presented by granulation tissue of proliferating fibroblasts and macrophages. Determined capillaries and vessels sine wave type with a well-formed vascular wall, which is composed of endothelium and basement membrane in the wall of the vessel entrance is t smooth muscle cells. In the area of the scar is determined moderate lymphocytic infiltration and macrophages in moderation. On the lateral wall of the right ventricle cardiomyocytes is not damaged, but the vessels Indonesia full-blooded, gleams them expanded.

Treatment of experimental myocardial infarction in rats after simulation-based medical intervention, characterized in that after creating a model of myocardial infarction perform intravenous immunocorrector Tamarit in the dosage 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 are judged on the adequacy and effectiveness of the treatment.



 

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