Mortality after coronary artery occlusion in different models of cardiac hypertrophy in rats.
Chronic treatment with minoxidil induces cardiac trophic and sympathetic responses, which may increase the propensity for lethal arrhythmias. To test this hypothesis, acute coronary artery occlusion was performed in conscious normotensive rats treated for 2 or 5 weeks with minoxidil with the use of a 2-stage approach to cause a myocardial infarction. For comparison, rats with aortocaval (A-V) shunts and spontaneously hypertensive rats (SHR) were studied. Minoxidil increased left ventricular and right ventricular weights by 15% to 20%, and the A-V shunt increased these weights by 30% to 40%. In SHR, left ventricular weight was increased by 50%, and right ventricular weight was increased by 25%. In rats treated with minoxidil for 5 weeks, coronary artery occlusion caused a rapid and marked mortality, and 4 hours after myocardial infarction, only 18% of these rats were alive versus 61% of the control rats. In rats with the A-V shunt, coronary artery occlusion was also associated with increased mortality, and after 6 hours, 33% were still alive compared with 59% of the control rats. In contrast, SHR with marked hypertension and cardiac hypertrophy showed only a minor increase in mortality (survival rates were 53% versus 60% in SHR versus Wistar-Kyoto rats, respectively). Mortality was preceded by high arrhythmia scores, and ventricular fibrillation was the cause of death. Discontinuation of minoxidil for 1 week, sympathetic blockade with nadolol or clonidine, or blockade of the renin-angiotensin system with enalapril or losartan did not improve minoxidil-induced excess mortality. We conclude that ventricular stretch and other mechanisms (eg, cardiac vagal activity) in rats appear to be more potent than hypertension-induced left ventricular hypertrophy in predisposing for lethal arrhythmias in the setting of acute ischemia.
Hypertension Unit, University of Ottawa Heart Institute, Ottawa, Ontario, Canada. fleenen@ottawaheart.ca
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Leenen
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Yuan
D000818:Animals; D001166:Arteriovenous Shunt, Surgical; D001794:Blood Pressure / Q000502:physiology; D006332:Cardiomegaly / Q000209:etiology / Q000503:physiopathology*; D003327:Coronary Disease / Q000401:mortality* / Q000503:physiopathology; D003331:Coronary Vessels / Q000503:physiopathology / Q000601:surgery; D004195:Disease Models, Animal; D004562:Electrocardiography; D006339:Heart Rate / Q000502:physiology; D006973:Hypertension / Q000503:physiopathology; D008026:Ligation; D008297:Male; D008914:Minoxidil / Q000008:administration & dosage; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017208:Rats, Wistar; D015996:Survival Rate
D008914:Minoxidil