Complex electrophysiological study of the effects of quaternidine carried out on intact hearts from cats, myocardial fragments from rats, and single ionic channels of large edible snail showed that quaternidine demonstrates properties of class 1B antiarrhythmic drug according to Vaughan-Williams nomenclature. This agent did not suppress nomotopic pacemaker automaticity, did not change conduction in ventricles, atria, and atrioventricular junction in hearts with preserved sinus rhythm, did not prolong refractoriness of the atria and atrioventricular junction, but prolonged efficient refractory period of heart ventricles. Quaternidine decelerated rapid depolarization of the action potential, but had no effect on its duration. It did not affect potassium conductance.

On the model of occlusion/reperfusion arrhythmia in cats it was shown that repeated injections of the NO-synthase inhibitor L-NAME decreased the incidence of occlusion arrhythmias (to 40%), eliminated reperfusion-induced ventricular fibrillation, and drastically reduced the latency of occlusion arrhythmias. A single injection of L-NAME (20 mg/kg) immediately before ligation of the coronary artery did not decrease the incidence of occlusion and reperfusion arrhythmias. Key Words: ventricular arrhythmias; nitric oxide; NO-synthase inhibitorNitric oxide (NO) is an intercellular transmitter, which affects various cell processes by modulating activity of metal-containing enzymes and formation of oxygen radicals [4]. NO is produced during conversion of arginine into citrulline catalyzed by constitutive and inducible isolbrms of NO-synthase (NOS). NO plays an important role in the ischemic pathology of the myocardium. There are experimental data on both protective and cytotoxic effects of NO [6,13]. The role of NO in the genesis of ischemia/reperfusion disturbances of the cardiac rhythm remains unclear, and experimental data are in many respects controversial [9,10,12,13].Our aim was to study the effect of a nonspecific inhibitor of NOS, N0~-nitro-L-arginine methyl ester (L-NAME) on the development of occlusion and reperfusion arrhythmias in cats. MATERIALS AND METHODSExperiments were carried out on 38 mature cats of both sexes weighing 2.5-3.5 kg. The descending branch of the left coronary artery was ligated for 30 min under Department of Faculty Therapy, Department of Cytology, Histology, and Embryology, N. P. Ogarev Mordovian State University, Saransk hexenal narcosis (40 mg/kg) and then the ligature was removed and perfusion was restored.In the present study we used L-NAME (Sigma), a non-specific inhibitor of NOS, which blocks the constitutive and inducible isotorms of this enzyme. In series I (n=5), L-NAME (20 mg/kg) was infused 10 min prior to applying the ligature. In series II (n=5), the inhibitor was injected intraperitoneally during 3 days (10 mg/kg/day) and intravenously on the 4th day (20 mg/kg) immediately before coronary occlusion.The control cats were injected with 0.9% NaCI. ECG was recorded during occlusion and 20 min of reperfusion. The data were statistically analyzed using the ~2 test. RESULTSIn the control series, ventricular extrasystole and tachycardia developed in all cats after ligating of coronary artery, in some cats fatal ventricular fibrillation was observed. When the coronary blood flow was restored, reperfusion arrhythmias appeared in 100% cals, and ventricular fibrillation in 65% cats (Table 1).Single injection of L-NAME immediately before ligation of the coronary artery did not change the incidence of arrhythmias and ventricular fibrillation during both during ischemia and reperfusion, which were 0007-4888/99/0005-0460522.00 e1999 Kluwer Academic/Plemml Publisllers

Depolarization automaticity was modeled on the papillary muscle from the guinea pig heart. Phosphoenolpyruvate (0.1 mM) 2-fold decreased the high-frequency calcium-dependent automaticity, but only weakly affected frequency of action potentials, whose upstroke was formed by fast sodium current or had a mixed nature. Phosphoenolpyruvate shifted the diastolic potential toward negative values, which depended on the amplitude of depolarization step. These effects developed 10-15 min after application of the preparation.Key Words: phosphoenolpyruvate; depolarization automaticity; action potential Glycolysis intermediates produced pronounced antiischemic and antiarrhythmic effect in animals with acute coronary occlusion and reperfusion [ 1,8,9,11 ]. Taking into consideration the involvement of cell metabolism in the genesis of cardiac arrhythmias [5,12], the antiarrhythmic effect of these substances can be explained by prolongation of the glycolytic energy production in cardiomyocytes [3,6,7]. However, participation of common electrophysiological mechanisms [13] in the antiarrhythmic effect of glycolysis intermediates was not yet assessed.Our aim was to study the effect of phosphoenolpyruvate (PEP) on electrical activity of isolated myocardial ventricles. MATERIALS AND METHODSThe study was carried out on guinea pigs weighing 250-350 g. The papillary muscles were isolated from the right ventricle under nembutal narcosis. The muscle were mounted in a chamber (2 ml) and perfused with oxygenated Tyrode solution (35~ pH 7.4) containing (in mM): 130 NaCI, 2.7 KC1, 2.0 CaCl2, 1.0 MgC12, 10 glucose, and 5 HEPES-NaOH.Membrane potential was measured with 10-20-M.Q glass microelectrodes. The signal and its first derivative were recorded with an automatic differentiator Department of Pharmacology, Mordovian State University, Saransk (Micromed). The duration of action potentials (AP) corresponding to 50 and 90% repolarization was measured. The preparations were stimulated with the trains of rectangular pulses applied via bipolar silver electrodes. The duration and frequency of pulses in the train were 1 msec and 1 Hz, respectively.The depolarization automaticity was modeled according to [2]. The rectangular direct current impulses were applied at a rate of 1 Hz via silver-chloride electrodes and an agar salt bridge from an ESU-2 electric stimulator (4.5-6.5 sec pulse duration), Membrane potential was recorded by the same method.In this study we used PEP tricyclohexylammonium salt (Sigma). RESULTSInitially we evaluated the effect of PEP on some parameters of AP in persistently stimulated guinea pig papillary muscle. PEP (0.1 mM) produced a moderate, but significant decrease in AP duration by l 1 and 7% at the 50 and 90% repolarization level, respectively. These changes developed 3-5 min after application of PEP in Tyrode solution and reached a steady-state level after 10-15 min. The PEP-induced shortening of AP became reversible only after 30-60-min washout. The test substance did not change resting potential, AP amplitude, and maxim...

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