The antiarrhythmic rhythmidazol produces a cardiotoxic effect that can be corrected by suphan, befol, and their combinations, as evidenced by normalization of ultrastructural organization of cardiomyocytes and myocardial oxygen consumption by these drugs. Key Words: antiarrhythmics; cardiotoxic effect; rhythmidazol; suphan; befolAlong with nominal therapeutic effects, antiarrhythmic drugs produce cardiotoxic effects (CTE) that manifest themselves in the appearance of new and in many cases fatal cardiac rhythm disturbances and in the inhibition of myocardial contractility [3,7,11].Morphological basis of CTE of antiarrhythmic drugs is provided by changes in myocardial ultrastructural organization (MUSO) [7,11], which are conjugated with ionic imbalance and disturbance of oxygen consumption in cardiomyocytes [1].Both the nonglycoside cardiotonic suphan (Nsuccine-dl-tryptophan dipotassium salt) and the reversible monoamine oxidase inhibitor antidepressant befol have pronounced cardioprotective effect against CTE of such standard antiarrhythmic drugs as procainamide, lidocaine, bonnecor, Obsidan, and verapamil [71.Thus, it seems worthwhile to study CTE of the new antiarrhythmic drug rhythmidazol (dihydrochloDepartment of Pharmacoiogy, Department of Hospital Therapy and Clinical Pharmacology, Kuban Medical Academy, Krasnodar; Department of Hypoxia Research, A. A. Bogomolets Physiology Institute, Kiev ride-9-diethylaminoethyl-2-tertiarobytilimidazo(1,2-a) benzimidazole), which according to classification [12] belongs to classes I and III antiarrhythmic drugs [5]. It should be necessary to test the possibility of correcting CTE of this antiarrhythmic drug by suphan, befol, and their combinations and to examine the effects of these preparations on MUSO and myocardial oxygen consumption. MATERIALS AND METHODSThe study was carried out on 427 conscious male albino rats. Combined action of rhythmidazol, befol, and suphan was tested by the method [10,11] with modifications [4]. The mean cardiotoxic doses (CTDs0) of the drugs were determined by their intravenous administration in doses provoking arrhythmia in 50% of animals. Arrhythmias were estimated by ECG (standard lead II), Befol, suphan, and their combinations in different doses (1/4, 1/2, 3/4, and 1 CTDs0 ) were administered 5 min prior to rhythmidazol. The ratio of the new CTDs0value to the control was taken as the protection coefficient (PC).The effects of the drugs on oxygen consumption and MUSO were studied in rats under acute hypoxia
Antidepressant befol, non-glycoside cardiotonic suphan, and their combinations were shown to have different ability to decrease cardiotoxic (arrhythmogenic) effect of novocainamide, lidocaine, bonnecor, obsidan, cordarone, verapamil, and rhythmidazol.
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