Martorana P A, Linz W, Göbel H, Petry P, Schölkens B A
Cassella AG, Frankfurt/M., F.R.G.
Eur J Pharmacol. 1987 Nov 17;143(3):391-401. doi: 10.1016/0014-2999(87)90463-8.
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.
在离体工作大鼠心脏和麻醉大鼠中研究了新型抗心律失常药物尼卡诺尔对冠状动脉闭塞和再灌注心律失常的影响。在离体工作大鼠心脏中，尼卡诺尔（10⁻⁶ M、5×10⁻⁶ M和10⁻⁵ M）可诱导与浓度相关的对再灌注心律失常的保护作用，且不改变心脏动力学，但在最高浓度时心率会降低。冠状动脉流出液中的酶水平（乳酸脱氢酶和肌酸激酶）以及心脏组织中的糖原、乳酸、三磷酸腺苷和磷酸肌酸浓度不受尼卡诺尔影响。给麻醉大鼠静脉注射尼卡诺尔（5和10 mg/kg）后，在闭塞后早期（0 - 30分钟），出现室性早搏（PVCs）和室性心动过速的动物百分比剂量依赖性降低，同时完全预防了心室颤动的发生。在再灌注期，接受5 mg/kg治疗的动物无一出现PVCs（此期观察到的唯一心律失常形式），接受10 mg/kg治疗的大鼠中有12%出现PVCs，而对照组大鼠为60%。两种剂量的尼卡诺尔均导致心率、血压和心肌耗氧量降低。梗死心肌质量与心室质量之比在5 mg/kg剂量时显著降低20%，在10 mg/kg剂量时降低28%。尼卡诺尔可能对预防和治疗与急性心肌梗死相关的心律失常有用。
