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.
It is reputed that the ideal therapeutic approaches to treatment of patients with acute coronary syndrome (ACS) and myocardium infarction (MI) should be aimed at the inflammation reaction triggers. This study investigated the effectiveness of the impact of L- 17 compound of the group of 5- phenyl substituted-6H-1,3,4-thiadiazine-2-amines upon the course of experimental MI as compared to the impact of a preparation, officially registered in Russia as an immunomodulator, Tamerit, belonging to phthalhydrazid derivative substance. Acute MI in rats was induced by left coronary artery coagulation. Histological study of the myocardium sections and biochemical analysis has been carried out at the 1st and 7th days of the experimental MI. The conducted investigations have shown that under the action of immunocorrectors the inflammation reaction character changes, exudative/destructive inflammation is replaced by a proliferative-cellular one. Animals' blood biochemical analysis at the background of L-17 and Tamerit introduction has shown a decrease of aminotransferases and lactatedehydrogenases activity in blood as compared to the reference group of animals' indicators, which is evidently caused by epicardial injury of myocardium and lesser amount of the alternative cardiomyocytes. At the same time, no noticeable difference in biochemical characteristics in groups, having been treated to immunomodulators of different chemical composition was identified, which is the sign of the essential similarity of their impact. Thus, immunocorrectors of different chemical groups (Tamerit and compound L17) diminish the volume of initial myocardial infarction and accelerate the granulation processes in course of MI, and represent a new category of treatment agents.
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 immune response and the plasma level of circulating cytokines in acute myocardial infarction (MI) in rats. The study was based upon experimental work which demonstrated the role of local and systemic inflammatory reactions in MI. Acute MI in rats was induced by left coronary artery coagulation. Histological study of the myocardium sections has been carried out at the 1(th) and 7(th) days of the experimental myocardial infarction. Serum activity of creatine phosphokinase (CPK), aspartate aminotransferase (AST), isoenzymes 1 and 2 and lactate dehydroge nase (LDH1-2) were investigated at days 1(st)and 7(th). ELISA analysis for plasma cytokine levels was performed using commercially available test kits following the manufacturer's instructions. Biochemical analysis in animals with the administration of the L-17 compound after MI showed that the AST and CPK levels at days 5 and 7 of experiments did not differ significantly from the values of intact animals. In animals of the group with MI without the administration of the L-17 compound, the IL-1 level 8 times and the TNF level 7.8 times exceeded the normal indicators, while the use of L-17 compound in the therapy resulted in only 1.8 times increase of IL-1 level and 4.7 times increase of TNF level in comparison with the norm. Thus, the introduction of L-17 compound in case of experimental MI delays exudative/alternative phase of inflammation, accelerates granulocytic and decreased the inflammation and anti-inflammation interleukins level.
Based on hypotheses concerning the role of stress in acute pancreatitis development, the experimental approach for the decrease stress damage via the use the compound with proven antistress/neuroleptic action was conducted. The study was aimed to discover 2-morpholino-5-phenyl-6H-1,3,4-thiadiazine hydrobromide (compound L-17) therapeutic action in experimental acute pancreatitis. The experimental model used was the ligation model. The trial was carried out on 50 male Wistar rats with average body weight 180-240 g. Histological picture of the pancreas was studied and biochemical and enzyme-immunoassays were carried out on the first and seventh days. The significant reduction in mortality on the background of L-17 compound administration was observed. While levels of all cytokines increased in induced experimental acute pancreatitis groups, the cytokine level rise was decreased when compound L-17 was administered. On the cellular level, the study revealed L-17's ability to prevent granulocytosis and decrease granulocytes infiltration to inflammatory foci. The decrease in inflammatory reaction magnitude and prevention of abscess formation in experimental acute pancreatitis accompanied by sistemic inflamamtion was due to L-17's ability to reduce neutrophilia and neutrophil entry into the injury zone.
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 possibility of inflammatory reaction evolvement correction in experimental acute pancreatitis. The study was based upon recent clinical and experimental work which demonstrated the role of local and systemic inflammatory reactions in pancreatonecrosis. Pancreatonecrosis modeling in rats was performed in accordance with the author’s modification of ligation model of acute pancreatitis. The biochemical and hematological analysis were performed in all groups at day 1. For microscopic analysis, five histological slices of each animal were analyzed. The main group, consisting of 15 animals with the average body weight 223 g each, got intraperitoneal injection of L-17 compound, dozed 40 mg/kg in an hour after surgery of pancreatitis formation. Later on, a 40 mg/kg doze of L-17 compound was repeatedly injected as often as once every 24 hours. Already during the 1st day of the experiment, no leucopenia was observed and the signs of proliferative inflammation were detected. Later, at the background of L-17 compound introduction (5th day of the experiment) the necrosis area got surrounded by demarcation bank, and further on (by the 7th day) had been entirely replaced by granulation tissue. Thus, the application of L-17 compound in experimental acute pan-creatitis results in replacement of destructive purulent inflammation by exudative-proliferative one, prevents lympho- and monocytopenia development, minimizes amylase and pancreatic ferments level during the first day of development of the disease and cuts down the lethality rate as result of pancreatonecrosis complications twofold
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