[Protective action of a modified fragment of galanine in rats with doxorubicin-induced heart failure]. / Zashchitnoe deistvie modifitsirovannogo fragmenta galanina pri serdechnoi nedostatochnosti u krys, vyzvannoi doksorubitsinom.

The use of the anticancer drug doxorubicin (Dox) is limited due to its cardiotoxic effect. Using the method of automatic solid-phase peptide synthesis, we obtained a synthetic agonist of galanin receptors GalR1-3 [RAla14, His15]-galanine (2-15) (G), exhibiting cardioprotective properties. It was purified by high performance liquid chromatography (HPLC). The homogeneity and structure of the peptide was confirmed by HPLC, 1H-NMR spectroscopy and mass spectroscopy. The purpose of this study was to study the effect of G on the metabolism and cardiac function of rats with chronic heart failure (CHF) caused by Dox. Experiments were performed using male Wistar rats weighing 280-300 g. The control group of animals (C) was intraperitoneally treated with saline for 8 weeks; the doxorubicin group (D) of rats was intraperitoneally treated with Doх; the group of Doх + peptide G (D+G) received intraperitoneally injections of Doх and subcutaneously injections of peptide G; the peptide G group (G) was subcutaneously treated with G. At the beginning and at the end of the study, the concentration of thiobarbituric acid reactive substances (TBARS) and the activity of creatine kinase-MB (CK-MB) were determined in blood plasma; the animals were weighed, and cardiac function was assessed using echocardiography. At the end of the experiments, the hearts were used for determination of metabolites and assessment of oxidative phosphorylation in mitochondria. After 8-week treatment, animals of group D were characterized by severe heart failure, the lack of weight gain and an increase in plasma TBARS concentration and CK-MB activity. These disorders were accompanied by a decrease in the content of myocardial high-energy phosphates, a reduction inmitochondrial respiratory parameters, accumulation of lactate and glucose in the heart, and disturbances in the metabolism of alanine and glutamic and aspartic acids. Coadministration of G and Dox prevented the increase in plasma CK-MB activity and significantly reduced the plasma TBARS concentration. At the end of the experiments animals of group D+G had higher myocardial energy state and the respiratory control index of mitochondria than animals of group D, there was a decrease in anaerobic glycolysis and no changes in the amino acid content compared to the control. The peptide G significantly improved the parameters of cardiac function and caused weight gain in animals of group D+G in comparison with these parameters in group D. The obtained results demonstrate the ability of a novel agonist of galanin receptors GalR1-3 to attenuate Dox-indiced cardiotoxicity.

[Metilin Improves Сardiac Function in Rabbits With Chronic Heart Failure].

AIM: To study effects of intravenous infusion of a cardioprotective drug metilin, developed at the "National Medical Research Center of Cardiology" on indices of cardiac function in rabbits in vivo after prolonged administration of doxorubicin. MATERIALS AND METHODS: Animals of the experimental group were intravenously injected with doxorubicin (2 mg / kg once a week) for 8 weeks, animals of the control group received the same volume of saline. Myocardial damage was characterized by an increase in concentration of malondialdehyde (MDA), troponin (TnI) and MB-fraction of creatine kinase (CK-MB) in venous blood and by disturbances in the left ventricle (LV) structure at morphological examination. Metilin effects on cardiac function were assessed by echocardiography and LV catheterization by the Millar catheter tip pressure transducer. RESULTS: Doxorubicin administration led to a decrease of the body mass of animals, an increase of the plasma concentration of cardiac markers CK-MB and TnI, lipid peroxidation (LPO) product MDA in venous blood, and pronounced disturbances in the structure of LV fibers and microvessels. At the same time, a significant decrease of myocardial contractility indices was observed. Manifestations of this decrease were increase of the end-diastolic and end-systolic dimensions (EDD and ESD, respectively), and decreases in the shortening fraction and ejection fraction (SF and EF, respectively) compared to baseline values. These changes indicated development of chronic heart failure (CHF) in animals of the experimental group. Against this background, intravenous infusion of metilin significantly increased SF and EF, but did not affect the heart rate. Beneficial effects of metilin on the indices of cardiac contractility and relaxation were maintained after the infusion was stopped. Noteworthy, metilin exerted greater influence on cardiac function of rabbits with CHF compared to control animals that did not receive doxorubicin. CONCLUSION: The obtained results indicate the potential of metilin to reduce LV dysfunction during chemotherapy with doxorubicin.

[Pathophysiological aspects of wound healing in normal and diabetic foot].

The main cause of long-term healing of ulcers in patients with diabetic foot is considered to be direct mechanical damage when walking due to reduced sensitivity to due to neuropathy, hyperglycemia, infection and peripheral artery disease. These factors determine the standard approaches to the treatment of diabeticfoot, which include: offloading, glycemic control, debridement of ulcers, antibiotic therapy and revascularization. Recently, however, disturbances in the healing process of the skin in diabetes recognized an additional factor affecting the timing of healing patients with diabetic foot. Improved understanding and correction of cellular, molecular and biochemical abnormalities in chronic wound in combination with standard of care for affords new ground for solving the problem of ulcer healing in diabetes.