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
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