Modulation of Inflammatory Response Improves Myocardial Infarct Healing in Rats

Abstract

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.

Effects of a compound from the group of substituted thiadiazines with hypothermia inducing properties on brain metabolism in rats, a study in vivo and in vitro

“…Previously L-17 compound was shown to benefit recovery after experimentally induced cardiac infarction and pancreatitis in rats [20–22]. Apart from these properties, we have confirmed that L-17 acutely reduces body temperature in rats.…”

“…Moreover, in vivo studies have shown anti-inflammatory activity of 1,3,4-thiadiazine derivatives (2-morpholino-5-phenyl-6H-1,3,4-thiadiazine hydrobromide, compound L-17) in experimental acute pancreatitis [20] and experimental cardiac infarction [21–22]. One of the most interesting effects of L-17 intraperitoneal injection is to reduce mouse body temperature (unpublished data, Boiko ER et.…”

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

“…Our earlier studies confirmed that some substituted 5R1, R62, 3,4-thiadiasine-2-amine compounds can induce cellular responses in the form of destructive types of inflammation and of activation of cellproliferative inflammation in the course of experimental myocardial infraction and acute pancreatitis [62,63]. Moreover, as was found in our previous studies, introduction of L17 in experimental pancreatic necrosis inhibited the increase in interleukins (IL-1α: 2.8 times, IL-6: 2.5 times, IL-10: 45.5 times) compared to the level of interleukins in untreated animals with experimental pancreatic necrosis [93].…”

“…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].…”

Effects of 1,3,4-thiadiazine compound with antidepressant properties in ligation model of acute pancreatitis

“…Administration of the tested compounds significantly changed the systemic inflammatory response pattern on the first experimental day, reduced mortality rates and lowered cytokine levels (Rantsev et al 2013). Similar changes were observed after the administration of these compounds in experimental myocardial infarction (Sarapultsev et al 2014). The common dominant role of inflammation and stress reaction in both pathogeneses indicates that stress modulation is a key mechanism in 1,3,4-thiadiazine action.…”