The effect of the novel antiarrhythmic agent
nicainoprol on
coronary occlusion and reperfusion
arrhythmia was investigated in isolated working rat hearts and in anesthetized rats. In isolated working rat hearts
nicainoprol (10(-6) M, 5 X 10(-6) M and 10(-5) M) induced concentration-related protection against reperfusion
arrhythmia without changing the cardiodynamics, with the exception of a decrease in heart rate at the highest concentration.
Enzyme levels (
lactate dehydrogenase and
creatine kinase) in the coronary venous effluent, and cardiac tissue concentrations of
glycogen,
lactate,
ATP and
creatine phosphate were not affected by
nicainoprol. Given to anesthetized rats,
nicainoprol (5 and 10 mg/kg i.v.) reduced dose dependently in the early post occlusion (0-30 min) period, the percentage of animals with premature ventricular complexes (PVCs) and
ventricular tachycardia while completely preventing the occurrence of
ventricular fibrillation. In the reperfusion period no animal treated with 5 mg/kg and 12% of the rats treated with 10 mg/kg showed PVCs (the only form of
arrhythmia observed in this period) versus 60% of the control rats. Both doses of
nicainoprol induced a decrease in heart rate, blood pressure and myocardial oxygen consumption. The ratio of
infarct mass to ventricular mass was significantly reduced by 20% at a dose of 5 mg/kg and by 28% at the dose of 10 mg/kg.
Nicainoprol could be useful in the prevention and treatment of arrhythmias associated with acute
myocardial infarction.