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Background: Metabolic and structural changes in cardiomyocytes in diabetes mellitus lead to aggravation of contractile myocardial dysfunction in coronary heart disease (CHD). The contractility dysfunction of cardiomyocytes is determined by a change in the levels of sarcoplasmic reticulum (SR) Ca2+-ATPase and energetic supply of the cardiomyocytes. Aims: To study the features of functional remodeling of the heart muscle in coronary heart disease with and without type 2 diabetes mellitus (DM2) depend on the level of Ca2+-ATPase and the activity of enzymes involved in energy metabolism. Materials and methods: The work was performed on the heart biopsy of patients with CHD and patients with CHD combined with DM2. The inotropic reaction of myocardial strips on rest periods was assessed. The expression level of Ca2+-ATPase, the activity of enzymes succinate dehydrogenase (SDH) and lactate dehydrogenase (LDH) and the intensity of oxidative phosphorylation processes were determined. Results: The interval-force relationship in patients with CHD with and without DM2 had both negative and positive dynamics. The positive dynamics corresponds to the "high content" of the Ca2+-ATPase and the negative dynamics corresponds to the "low content" were found. At the combined pathology the positive inotropic dynamics is more pronounced and corresponds to a higher protein level. In the patients myocardium with CHD the activity of SDH and LDH was higher, while the oxygen uptake rate by mitochondria was higher in the myocardium with combined pathology. Conclusions: The potentiation of inotropic response of patient myocardium with CHD with and without DM2 corresponds to the "high level" of Ca2+-ATPase. In the combined pathology the inotropic capabilities of the myocardium are more expressed. In CHD the synthesis of ATP in cardiomyocytes is realized mainly due to glycolytic processes and Krebs cycle. In combined pathology the ATP synthesis is realized to a greater extent due to the oxidative phosphorylation.

Background : one of the reasons of violation of the functional viability of the myocardium is considered to be the shortage oxygen and energy of the myocardium. Its reason is the inhibitory effect of fatty acids on glucose oxidation. Recently, however, new data have been published, proving the need for and importance of fatty acids in the maintenance and regulation of the functional activity of the myocardium in chronic pathology. Objective : to investigate the influence of free polyunsaturated and saturated fatty acids (FA) on the oxygen uptake of isolated cardiomyocytes in intact rats and animals with ischemic or diabetic heart disease. Methods : executed non-randomized controlled study. Considered 3 groups of male rats of Wistar line (weight 250-300 g) with 10 animals in each group. Myocardial infarction ("heart attack") caused by ligation of the left coronary artery, and diabetes ("diabetes") – intraperitoneal injection of streptozotocin. The group "control" was presented intact animals. Myocardial infarction caused by ligation of the left coronary artery, and diabetes by intraperitoneal injection of streptozotocin. Isolated cardiac myocytes were obtained by enzymatic method. Oxygen consumption was assessed polarographically at different saturation incubation medium with oxygen ([O2] £8 mg/l and ([O2] ≥16 mg/l). Results : As the fatty acid used arachidonic and palmitic acid. It is established that the introduction to the incubation medium 20 μm arachidonic or palmitic fatty acid significantly increased the oxygen consumption of intact cardiomyocytes of rats. Both at the ischemic and at diabetic defeat of heart was obtained the opposite result. The most pronounced decrease of oxygen consumption are shown in diabetes mellitus. Conclusion : Conclude that the inhibitory effect of LCD on the rate of oxygen consumption during the at the ischemic and at diabetic defeat of heart may be due to their influence on the barrier function of mitochondrial membranes of cardiomyocytes, the activity of membrane-associated enzymes and their associated processes.

It was shown that the energy metabolism of the heart mitochondria of experimental animals and patients is more resistant to damage at combined postinfarction cardiosclerosis and diabetes in comparison with the individual pathology. We found that the changes of free fatty acid content and conjugation of the processes of oxidation and phosphorylation in heart mitochondria are components of the metabolic stability of myocardium at the combined development of postinfarction cardiosclerosis and diabetes mellitus. Our data demonstrate a direct link between the violations of the processes of oxidative phosphorylation and accumulation of free fatty acids owing to change in activity of endogenous phospholipases, in particularly, mi- tochondrial phospholipase A2. Similar results were obtained for intraoperative biopsy specimens of patients’ hearts, and of adult Wistar rats’ hearts. We hypothesized that the preservation of energy metabolism is a manifestation of summing up of compensatory processes at de- velopment of nonspecific response of cells to damage at the early stages of pathological pro- cess.

We studied the rate of oxygen consumption by isolated cardiomyocytes from intact rats and animals with experimental myocardial infarction or streptozotocin-induced diabetes mellitus. The measurements were performed in standard incubation medium under various conditions of oxygenation and after addition of arachidonic acid (20 μmol/liter). Under normoxic conditions, arachidonic acid improves respiration of cardiomyocytes from intact animals, but reduces this parameter in cells isolated from animals with pathologies. The intensity of O2 consumption by cardiomyocytes from intact rats and animals with pathologies was shown to decrease during hypoxia. Addition of arachidonic acid aggravated inhibition of respiration for cardiomyocytes from intact rats and specimens with myocardial infarction, but had no effect in diabetes mellitus. The effect of arachidonic acid on oxygen consumption rate is probably mediated by a nonspecific mechanism realized at the mitochondrial level.

Comparative study of changes in myocardial activity of lactate dehydrogenase (LDH), succinate dehydrogenase (SDH), and capillary density distribution in the experimental models of diabetic and postinfarction damage of rat heart was performed. Data showed that decrease in LDH and SDH activities was observed in both pathologies which can suggest abnormal processes of glycolysis and oxidative phosphorylation in cardiac mitochondria. Activity of LDH and SDH in combined pathologies was comparative with the corresponding values of these parameters in control group. The authors hypothesize that these differences can be caused by specifics of myocardial vascularization. The results of the study showed that an increase in capillary density was found in all groups of rats with pathologies compared with control group. However, no significant differences in the intensity of angiogenesis processes were found between groups with pathologies.