BACKGROUND: Various angiotensin-converting enzyme inhibitors are known to improve heart function and prolong survival in patients and animals after myocardial infarction. Because myocardial infarction is known to induce arrhythmias, this study tested the hypothesis that early treatment with the angiotensin converting enzyme inhibitor imidapril reduces mortality during acute myocardial infarction because of protective effects against arrhythmogenesis. METHODS AND RESULTS: Rats were randomly divided into four groups: sham control, myocardial infarction, sham plus imidapril, and myocardial infarction plus imidapril. Myocardial infarction was produced by ligation of the left anterior descending coronary artery. Treated rats received imidapril (1 mg/kg/day) through a gastric tube beginning 1 hour after coronary occlusion; control rats received tap water. Electrocardiogram (ECGs) were recorded 1, 3, 7, and 21 days postocclusion. Infarct size and scar weight were determined at 21 days in the myocardial infarction groups with and without imidapril treatment. ECGs of untreated rats showed ST-segment changes, abnormal Q waves, premature ventricular complexes, and QT(c) prolongation 1-21 days after coronary occlusion. Total mortality in 21 days averaged 35% in untreated rats; mortality within 48 hours was 30%. On the other hand, imidapril-treated rats showed fewer ST-segment changes, fewer abnormal Q waves, and a decreased incidence of premature ventricular complexes after coronary occlusion; the ST-segment and QT(c) interval returned to basal values within 1 week after occlusion. Imidapril treatment did not affect the ECG pattern in sham-treated control animals. Total mortality in the imidapril-treated group in 21 days after infarction was 22.5%; mortality within 48 hours was 20% (P <.05 compared with the untreated infarction group). Infarct size and scar weight caused by coronary occlusion did not differ in the untreated and imidapril-treated groups. CONCLUSIONS: Early treatment with imidapril markedly decreases mortality in rats after acute myocardial infarction. The lower mortality is not associated with a decrease in infarct size but is consistent with a protective effect of the drug against arrhythmogenesis.
BACKGROUND: Various angiotensin-converting enzyme inhibitors are known to improve heart function and prolong survival in patients and animals after myocardial infarction. Because myocardial infarction is known to induce arrhythmias, this study tested the hypothesis that early treatment with the angiotensin converting enzyme inhibitor imidapril reduces mortality during acute myocardial infarction because of protective effects against arrhythmogenesis. METHODS AND RESULTS:Rats were randomly divided into four groups: sham control, myocardial infarction, sham plus imidapril, and myocardial infarction plus imidapril. Myocardial infarction was produced by ligation of the left anterior descending coronary artery. Treated rats received imidapril (1 mg/kg/day) through a gastric tube beginning 1 hour after coronary occlusion; control rats received tap water. Electrocardiogram (ECGs) were recorded 1, 3, 7, and 21 days postocclusion. Infarct size and scar weight were determined at 21 days in the myocardial infarction groups with and without imidapril treatment. ECGs of untreated rats showed ST-segment changes, abnormal Q waves, premature ventricular complexes, and QT(c) prolongation 1-21 days after coronary occlusion. Total mortality in 21 days averaged 35% in untreated rats; mortality within 48 hours was 30%. On the other hand, imidapril-treated rats showed fewer ST-segment changes, fewer abnormal Q waves, and a decreased incidence of premature ventricular complexes after coronary occlusion; the ST-segment and QT(c) interval returned to basal values within 1 week after occlusion. Imidapril treatment did not affect the ECG pattern in sham-treated control animals. Total mortality in the imidapril-treated group in 21 days after infarction was 22.5%; mortality within 48 hours was 20% (P <.05 compared with the untreated infarction group). Infarct size and scar weight caused by coronary occlusion did not differ in the untreated and imidapril-treated groups. CONCLUSIONS: Early treatment with imidapril markedly decreases mortality in rats after acute myocardial infarction. The lower mortality is not associated with a decrease in infarct size but is consistent with a protective effect of the drug against arrhythmogenesis.