Prolonged immobilization stress activates lipid peroxidation, causes ischemic damage to the myocardium, and promotes the development of some manifestations of atherosclerosis in rabbits. Intravenous infusion of cytochrome c (1 mg/kg) during 30 days of immobilization lowers the extent of lipid peroxidation and produces cardio-and endothelium-protective effects.Key Words: prolonged immobilization stress; cytochrome c; arteriosclerosisThe development of poststress complications caused by prolonged influence of damaging factor is a consequence of exhaustion of compensatory mechanisms (phase III of stress according to Selye) leading to irreversible changes in the organism and diseases [6]. Therefore, prevention of stress and poststress changes is an important problem. It is known that hypoxia is a damaging factor in stress of any genesis. Consequently, antihypoxants are prospective candidates for stress-controlling drugs. In the present study we examined the effect of cytochrome c on adaptational processes, namely, lipid peroxidation (LPO) under conditions of prolonged immobilization stress. MATERIALS AND METHODSThe study was carried out in summer. Twenty male Chinchilla rabbits weighing 2-3 kg were used. Chronic immobilization stress (30 days) was modeled by placing the animals in small cages. Control group consisted of 12 rabbits. Starting from the second day of immobilization, experimental rabbits (n=8) were administered cytochrome c (1 mg/kg, daily, into the marginal ear vein). Electrocardiogram (ECG) was recorded before and 30 days after stress. RESULTSProlonged immobilization stress had a negative effect on general condition of the animals and caused 20% lethality. The rabbits died predominantly from acute cardiac insufficiency, pulmonary edema, and infarction and congestion pneumonia. Most rabbits (70%) died within 7-14 days of immobilization.Severe hypodynamia ted to activation of LPO, as evidenced by increased plasma content of MDA by 98.7, 142.2, and 127.7% on days 7, 14, and 30, respectively (Table 1). A similar dynamics of MDA content was observed in erythrocytes: an increase by 51.3 and 92.9% on days 7 and 14. By the 30th day, the MDA content dropped in erythrocytes but remained high in the plasma, which is probably due to the outflow of LPO products from damaged tissues. Activation of LPO in the blood led to myocardial damage. On day 30, 58% of the rabbits developed myocardial infarction (the presence of the Q wave) and 35% of them developed myocardial ischemia (displacement of the R-ST interval). Pathomorphological changes in the aorta were observed in all rabbits: in 44% of the rabbits they were severe and destructive (thinning of the aortic wall, aneurisms, ulcers, and multiple plaques), in 33% the changes
Increased level of the products of lipid peroxidation (LPO) is considered a factor leading to the risk of atherosclerosis development [1][2][3]. At the same time, experimental investigations confirm the ability of antioxidants to produce positive effects with respect to appearance and development of the atherosclerosis process [4][5].As is known, a significant role in pathogenesis of a number of diseases involving increased LPO level as a general pathogenic factor may belong to chronic stress. The results of some investigations showed that antioxidants such as emoxypine and mexidol may offer protection against acute stressor damage [6,7]. The purpose of this study was to characterize the antioxidant and hypolipidemic properties of mexidol and emoxypine on the model of prolonged immobilization-induced stress. EXPERIMENTAL PARTExperiments were performed on a group of 33 sexualy matore male Chinchilla rabbits weighing 2-3 kg. The immobilization-induced stress in the test animals was achieved by holding them in wire-framework cages, which strongly restricted the mobility but did not hinder access to food and water.There were three series of experiments. The control group of 12 rabbits was kept under the strong hypodynamia conditions for 30 days. Animals in the second (12 rabbits) 231and third (9 rabbits) groups were kept during the same period under identical conditions and daily injected in their edge auricular (otic) veins with 1 mg/kg of emoxypine or mexidol, respectively. Both before the mobility limitation and in the course of the experiment (7th, 14th, and 30th days) blood samples were taken and the plasma and erythrocytes were analyzed for malonic dialdehyde (MDA, the final LPO product) using a thiobarbitufic acid test. Erythrocytes were also analyzed for glutathione peroxidase (GP) [8], catalase [9], and superoxide dismutase (SOD) [10]. The total blood serum cholesterol was determined according to [I 1], the content of low-density lipoproteins (LDLs) was studied turbodimetritally [12], the total lipid and triglyeeride levels were determined using the standard reagent kits (Sigma, USA), highdensity lipoproteins (HDLs) were analyzed after heparinmanganese precipitation and the deposition of apoprotein-I 3-containing lipoproteins (apo-~Ls) according to [11], and the blood serum albumin was determined by electrophoresis in agar. After the immobilization period, the animals were killed by intravenous injection of a lethal dose of hexenal (100 mg/kg). The results of investigation were processed by methods of variational statistics with determination of the Student t-criterion. RESULTS AND DISCUSSIONProlonged immobilization-induced stress resulted in a high level of lethality (24 %) in the control group of animals.The immobilization leads to activation of the LPO process, as indicated by increasing MDA level in the blood plasma (by 99, 144, and 128 % on the 7th, 14th, and 30th day, respectively) and, albeit to a lower extent and within a
In rats with dyslipidemia epinephrine decreased HR and suppressed automaticity of the sinus node. This effect was not eliminated by LBK-149, dibunol, and glutabiance despite normalization of the plasma lipid spectrum. LBK-149 prevented the development of heart rhythm disturbances during epinephrine administration.
Antiarrhythmic activity of lidocaine during early occlusion and reperfusion arrhythmias decreased in rats with experimental disturbances in lipid and carbohydrate metabolism. The course of additional treatment with compound LBK-149 potentiated antiarrhythmic activity of lidocaine.
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