Angioline Influence on the Cardio and Systemic Hemodynamics Markers in the Rabbits with Chronic Cardiac Insufficiency

During the experiments on rabbits with chronic cardiac insufficiency simulation, modeled by intravenous doxorubicin cardiovascular abnormalities and systemic hemodynamics, next results were established. Angioline usage at a dose of 100 mg/kg restored the parameters that characterize the contractile function of the heart and have advantages over endothelioprotector of indirect action by mildronat. Identifying the pathogenic targets in chronic cardiac insufficiency contributes to more effective searching drugs of targeted treatment of key indicators of myocardial metabolism function in order to improve the efficiency of this pathology treatment. In the chronic cardiac insufficiency cardio hemodynamic indicators are simultaneously being excited determining pumping heart function and in response to the decrease in cardiac output and systemic hemodynamics parameters associated with an increase in peripheral vascular resistance. Not only development of oxidative and nitrozyl stress was observed in this pathology, but also endothelial dysfunction which prevent adequate blood regulation, have deleterious effect on cell membranes and DNA structure, enzymes activity, electron transport the mitochondria and regulatory proteins in the cells. Taking into consideration that in chronic cardiac insufficiency decrease of nitrogen oxide bioavailability and increase of its degradation occur the drugs with endothelioprotective action have been examined. Inhibitors of APE, the blockers of angiotensin II receptors, metabolititropic drugs (meldonium, the derivatives of succinic acid, arginine) have indirect endothelioprotective action. In the research and production association, «Pharmatron» the direct endothelioprotector Angioline has been synthesized. Its action was examined on the nitrogenium oxydatum markers in the rat's myocardium in the chronic cardiac insufficiency. The purpose of the study is to examine the angioline influence on the cardio- and systemic hemodynamics in the rabbit's chronic cardiac insufficiency. Methods of research. Experiments were conducted on the Shinshilla rabbits, weighting 2,5-3,3 kg. Experiments were made based on European convention about common ethical principles regulations. During the experiment (narcosis: urethanum 1g/kg) after cateterisation of the left ventricle of heart the main parameters of cardio- and systemic hemodynamics have been registered – maximal pressure in the left ventricle (Pmax), systemic arterial pressure (SAP) frequency of heart contractions (FHC). All markers have been registered on the apparatus HPVIRIKAUA component Monitoring System (Hewlett Packard, Germany) and also cardiac index (CI), systolic index (SI), working stoke index of the left ventricle (WSILV), working index of left ventricle (WILV), stroke volume (SV), minute volume of blood (MVB), total peripheral vascular resistance (TPVR). The chronic cardiac insufficiency has been modulated by doxorubicine injection in cumulative dose of 15 mg/kg intravenously, divided in 6 injections during 6 days. Angioline has been injected 1 time per day intraperitoneally in the dose of 100 mg/kg as suspension with Twin-80 combining with doxorubicine per 14 days and then per 21 days also. Combining mildronat as the drug of comparing in the dose of 250 mg/kg has been injected intraperitoneally. There were four groups of rabbits: 1st group – 15 intact rabbits, 2nd group – controlled 6 rabbits with cardiac insufficiency, 3d group – 15 rabbits treated with angioline, 4th group – 6 rabbits treated with mildronate.