FAILURE OF NITRIC-OXIDE DONORS TO ALTER ARRHYTHMIAS INDUCED BY ACUTE MYOCARDIAL-ISCHEMIA OR REPERFUSION IN ANESTHETIZED RATS

1 The aim of the present studies was to examine the effects of nitric oxide donors on arrhythmias induced by coronary artery occlusion and r eperfusion, and on cardiac cyclic nucleotides. Experiments were perfor med in pentobarbitone-anaesthetized rats prepared for occlusion of the left coronary artery. 2 Sodium nitroprusside (0.1, 0.3 and 1 mu g kg( -1) min(-1)) had no significant effects on the incidence of ventricula r tachycardia, total ventricular fibrillation or the mortality resulti ng from 25 min of acute myocardial ischaemia when compared with values in controls. In addition, there was no alteration in the number of ve ntricular premature beats that occurred in survivors. 3 3-Morpholinosy dnonimine-N-ethylcarbamide (SIN-1, 10, 20 and 40 mu g kg(-1) min(-1) m in(-1)) caused marked hypotension but did not alter the incidence or s everity of ischaemia-induced arrhythmias. In rats subject to abrupt re perfusion after 5 min of myocardial ischaemia, lower doses of SIN-1 (1 , 3 and 10 mu g kg(-1) min(-1)) still caused significant reductions in systolic and diastolic blood pressure but were devoid of antiarrhythm ic activity. 4 In separate experiments in sham-operated rats, sodium n itroprusside (1 mu g kg(-1) min(-1)), isosorbide dinitrate (30 and 60 mu g kg(-1) min(-1)) and SIN-I (20 and 40 mu g kg(-1) min(-1)) had no significant effects on cardiac cyclic GMP content. 5 These results ind icate that nitric oxide donors do not alter arrhythmias induced by acu te coronary artery occlusion or reperfusion in anaesthetized rats. Alt hough increases in total cardiac cyclic GMP could not be detected, the results suggest that, at least in the rat, cyclic GMP does not influe nce these arrhythmias.