Under conditions of simulated circulation failure in rats ajmaline increases tolerance for strophanthin cardiotoxicity to a greater extent than trimecaine. In isolated preparations of frog myocardium both antiarrhythmic agents somewhat weaken the inotropic effect of the cardiac glycoside and virtually do not influence its chronotropic effect.

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

Data on the syntheses and structures of a series of new derivatives of 2-diethylamino-2¢,6¢-dimethylphenylacetamide are described. The results of an experimental study of the new compounds on various arrhythmia models in animals are presented. Several substances effectively preventing the onset of ventricular ischemia, reperfusive and toxic fibrillation, and ischemic arrhythmia have been selected, which are superior to the reference drug lidocaine with respect to their antiarrhythmic properties.

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