deGraeff P A, deLangen C D, van Gilst W H, Bel K, Scholtens E, Kingma J H, Wesseling H
Department of Pharmacology/Clinical Pharmacology, University of Groningen, The Netherlands.
Am J Med. 1988 Mar 11;84(3A):67-74. doi: 10.1016/0002-9343(88)90207-0.
The effects of the converting enzyme inhibitor captopril on the susceptibility of the heart to ventricular arrhythmias following ischemia, both in vitro and in vivo, were studied. In isolated rat hearts, captopril, administered either before or at the end of ischemia, reduced ventricular fibrillation upon reperfusion after 15 minutes of local ischemia. Reduction of purine overflow, improvement in contractility, and increase in coronary blood flow occurred concomitantly. In vivo, a closed-chest pig model was used to determine the effects of captopril, administered at the end of ischemia and continued orally, on the susceptibility to ventricular arrhythmias during the chronic phase of myocardial infarction. Myocardial ischemia was induced by 60-minute inflation of a balloon catheter in the left anterior descending coronary artery. Upon reperfusion, an accelerated idioventricular rhythm occurred, both in 10 untreated and in 10 captopril-treated animals. Creatine kinase levels during the reperfusion period were significantly lower after captopril treatment. Two weeks after the short-term experiments, monomorphic ventricular tachycardia could be induced with programmed electrical stimulation in six of eight surviving untreated pigs. In contrast, in none of the six surviving captopril-treated animals was ventricular tachycardia inducible. Thus, early intervention with captopril during the development phase of myocardial infarction may have beneficial effects on the subsequent development of ventricular arrhythmias. Salvage of ischemic myocardium, improvement in ventricular function, beneficial effects on coronary flow, and decreased activity of the sympathetic nervous system may all contribute.
研究了转换酶抑制剂卡托普利在体外和体内对心脏缺血后室性心律失常易感性的影响。在离体大鼠心脏中，无论是在缺血前还是缺血结束时给予卡托普利，均可减少局部缺血15分钟后再灌注时的心室颤动。同时出现嘌呤溢出减少、收缩性改善和冠状动脉血流量增加。在体内，采用闭胸猪模型来确定在缺血结束时给予并持续口服的卡托普利对心肌梗死慢性期室性心律失常易感性的影响。通过在左前降支冠状动脉中球囊导管充气60分钟诱导心肌缺血。再灌注时，10只未治疗动物和10只卡托普利治疗动物均出现加速性室性自主心律。卡托普利治疗后再灌注期间的肌酸激酶水平显著降低。短期实验两周后，8只存活的未治疗猪中有6只可通过程控电刺激诱发单形性室性心动过速。相比之下，6只存活的卡托普利治疗动物中无一例可诱发室性心动过速。因此，在心肌梗死发展阶段早期使用卡托普利可能对随后室性心律失常的发生有有益影响。挽救缺血心肌、改善心室功能、对冠状动脉血流的有益作用以及交感神经系统活性降低可能都有作用。
