STUDY OF MYOCARDIAL REMODELING MARKERS IN EXPERIMENTAL HISTOTOXIC HYPOXIA

Abstract

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Background. In modern works, there are isolated data concerning the problem of cardiac remodeling and fibrogenesis. Aim. The available data are ambiguous, so the goal of the study is to study the processes of fibrogenesis and inflammation in the myocardium of sexually mature rats. Material and Methods. The study was conducted on 25 mature male Wistar rats weighing 220- 310 g. The control group was represented by 5 intact animals. A solution of cobalt chloride for the modeling of histoxic hypoxia was introduced through an atraumatic probe into the stomach at a dose of 4 mg/ kg, daily once a day for 30 days. Results and Discussion. The conducted study showed that changes in the myocardium developed, which, according to morpho-functional manifestations, could be attributed to varieties of toxic cardiomyopathy. Hydrophobic dystrophy was observed in the cytoplasm of cardiomyocytes, myocytolysis foci appeared. Masson’s staining revealed an excessive amount of collagen fibers in the interstitium, and also in the perivascular space, which apparently made it more difficult to transport substrates and oxygen from the bloodstream to the working cells under hypoxic conditions. Perivascularly and in interstitium, intensely colored macrophages and fibroblasts appeared. Remodeling of the myocardium, which occurs during hypoxic damage, is accompanied by a reorganization of the connective tissue stroma. At the same time, the enzymatic cleavage of the previously existing connective tissue fibers develops and de novo synthesis of interstitial substance according to the new conditions of mechanical loads. The leading role in this process is assigned to the enzymes of the metalloproteinase group. Expression of MMP-9 metalloproteinase was characterized as weakly positive (+) and positive (++) in some parts of the myocardium. Increased expression of MMP-9 indicated activation of a systemic inflammatory response in case of myocardial damage. Conclusions. The leading trigger mechanism of fibrogenesis processes is necrosis of cardiomyocytes, leading to the launch of biochemical intracellular signaling processes that initiate a partial change in reparative processes. It is obvious that the development of interstitial fibrogenesis plays an important role in the pathophysiology of myocardial remodeling under conditions of hypoxia and may contribute to the progression of its dysfunction.