New insights in to the treatment of myocardial infarction

Abstract

This study investigated the effects of the L-17 compound of the group of substituted 5R1, 6H2-1,3,4-thiadiazine-2-amines on the inflammatory cellular infiltration and myocardial remodelling which occurs after acute myocardial infarction (MI) in rats. The study is based upon recent clinical and experimental work which demonstrated the role of local and systemic inflammatory reactions in postinfarction remodelling. Acute MI in rats was induced by left coronary artery coagulation. Animals were sacrificed on day one, five and seven after MI induction. The myocardiumal samples were taken from all parts of the heart and examined by histology. This included areas of infarction, infraction and areas that were peri-infarctiom and left ventricular areas distant from the damaged tissues. Serum activity of creatine phosphokinase (CPK), aspartate aminotransferase (AST), isoenzymes 1 and 2 and lactate dehydrogenase (LDH1-2) were investigated on the same three days, before and in the process of MI development was investigated (at days 1, 5 and 7). The L-17 compound to not only decreased the area of initial infarction but also changed the pattern of inflammatory reaction in the affected myocardium fundamentally. Laboratory studies of effects of L-17 compound on the development and course of experimental MI showed that administration decreased blood AST and CPK levels significantly and provided useful the data about the correlation between the activity of these enzymes and the dimensions of the significantly necrotic area. In this model of experimental MI the use of the L-17 compound induced led to the replacement of the exudative destructive inflammation that is seen under standard conditions with a more cellular "productive" pattern of inflammation, with associated reduction in initial necrosis area and the, decrease in myocardial ischaemia and reperfusion injury may account for the accelerated repair process.

The impact of immunomodulator compound from the group of substituted thiadiazines on the course of stress reaction

“…Compound L-17 reduced the severity of stress response manifestations that accompanied systemic inflammation; L-17 reduced levels of IL-6 and IL-10, reduced the severity of neutrophilia, increased levels of monocytes and leucocytes in blood [65], and reduced the flow of neutrophils while increasing the flow of monocytes/macrophages to areas of inflammation [62]. These data suggest that compound L-17 might possess anti-stress properties.…”

“…Our group demonstrated in earlier studies that the compound L-17 from the group of 5-phenyl substituted-6H-1,3,4-thiadiazine-2-amines, has an effect on the course and severity of experimental myocardial infarction [62,63] and acute pancreatitis complicated with systemic inflammation syndrome [64,65]. Compound L-17 reduced the severity of stress response manifestations that accompanied systemic inflammation; L-17 reduced levels of IL-6 and IL-10, reduced the severity of neutrophilia, increased levels of monocytes and leucocytes in blood [65], and reduced the flow of neutrophils while increasing the flow of monocytes/macrophages to areas of inflammation [62].…”

“…Test compounds L-17 from the group of 5-phenyl substituted-6H-1,3,4-thiadiazine-2-amines 1 studied in these experiments has been proven to have a biological effect [62,67]. The lethal dose of L-17 (LD50) is 434 mg/kg (by weight).…”

Cytokine Regulation of Regenerative Processes in Pancreatic Gland in Alloxan-Induced Diabetic Rats, and It Correction by 1,3,4-Thiadiazine Composition and Lipoic Acid

“…Тем не менее механизмы корригирующего влияния соединений ряда 1,3,4-тиадиазина при аллоксановом СД остаются недостаточно изу-ченными. Учитывая роль хронического низкоин-тенсивного системного воспаления в патогенезе СД, а также данные о противовоспалительном действии соединения ряда 1,3,4-тиадиазина на моделях экспериментального инфаркта ми-окарда [36] и панкреонекроза [16], представляет интерес оценить возможность коррекции реге-нераторных процессов в островковом аппарате поджелудочной железы и цитокинового профиля крови соединением ряда 1,3,4-тиадиазина при аллоксановом СД у крыс.…”

Donepezil Hydrochloride Mitigates Consequences of Acute Myocardial Infarction in Male Albino Rats

“…The disease is usually results from complete occlusion of a coronary artery with a thrombus with subsequent necrosis of myocardial tissue (Amsterdam et al, 2014). Inflammatory cellular infiltration and myocardial remodelling occurs after AMI with destructive and exudative inflammation, which leads to increase in the necrotic area (Sarapultsev et al, 2012). In human patients with myocardial infarction, defective suppression, and impaired resolution of inflammation may be important mechanisms in the pathogenesis of remodeling and in progression to heart failure (Frangogiannis, 2012) Association between Alzheimer Dementia (AD) and multiple cardiovascular risk factors such as hypertension, diabetes, atherosclerosis, dyslipidaemia and stroke has previously shown Normal functioning of the cardiovascular system depends on an adequate sympathetic-parasympathetic interaction.…”