Protective effects of captopril against ischemia/reperfusion-induced ventricular arrhythmias in vitro and in vivo.
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.
deGraeff
P A
PA
Department of Pharmacology/Clinical Pharmacology, University of Groningen, The Netherlands.
deLangen
C D
CD
van Gilst
W H
WH
Bel
K
K
Scholtens
E
E
Kingma
J H
JH
Wesseling
H
H
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000503:physiopathology*; D002216:Captopril / Q000494:pharmacology*; D002304:Cardiac Pacing, Artificial; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000150:complications* / Q000378:metabolism; D003402:Creatine Kinase / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013552:Swine
D002216:Captopril; D003402:Creatine Kinase