Effects of ACE inhibition and beta-receptor blockade on energy metabolism in rats postmyocardial infarction

Chronic treatment with beta-receptor blockers or angiotensin-converting enz yme (ACE) inhibitors in heart failure can reduce mortality and improve left ventricular function, but the mechanisms involved in their beneficial acti on remain to be fully defined. Our hypothesis was that these agents prevent the derangement of cardiac energy metabolism. Rats were subjected to myoca rdial infarction (MI) or sham operation. Thereafter, animals were treated w ith bisoprolol, captopril, or remained untreated. Two months later, cardiac function was measured in the isolated heart by a left ventricular balloon (pressure-volume curves), and energy metabolism of residual intact myocardi um was analyzed in terms of total and isoenzyme creatine kinase (CK) activi ty, steady-state levels (ATP, phosphocreatine), and turnover rates (CK reac tion velocity) of high-energy phosphates (P-31 nuclear magnetic resonance) and total creatine content (HPLC). Bisoprolol and partially captopril preve nted post-MI hypertrophy and partially prevented left ventricular contracti le dysfunction. Residual intact failing myocardium in untreated, infarcted hearts showed a 25% decrease of the total, a 26% decrease of MM-, and a 37% decrease of the mitochondrial CK activity. Total creatine was reduced by 1 5%, phosphocreatine by 21%, and CK reaction velocity by 41%. Treatment with bisoprolol or captopril largely prevented all of these changes in infarcte d hearts. Thus the favorable functional effects of beta-receptor blockers a nd ACE inhibitors post-MI are accompanied by substantial beneficial effects on cardiac energy metabolism.