EFFECTS OF LONG-TERM THERAPY WITH ACE-INHIBITORS, CAPTOPRIL, ENALAPRIL AND TRANDOLAPRIL, ON MYOCARDIAL ENERGY-METABOLISM IN RATS WITH HEART-FAILURE FOLLOWING MYOCARDIAL-INFARCTION

Although pharmacological therapy with angiotensin converting enzyme (A CE) inhibitors has proved to be effective in patients with heart failu re (HF), the experimental basis of this effect has not yet been addres sed. In the present study, animals with HF were treated with an oral a dministration of 10 mg/kg/day captopril, 10 mg/kg/day enalapril and 3 mg/kg/day trandolapril from the 2nd to 12th week after the operation, HF was induced by permanent occlusion of the left coronary artery of t he rat at 2 mm from its origin, Treatment of the HF rats with the ACE inhibitors enhanced the decrease in mean arterial blood pressure, atte nuated the rise in left ventricular end-diastolic pressure, an indirec t marker of preload, and diminished the reduction in cardiac output an d stroke volume indices of the HF animal, Treatment. also reversed the reduction in ATP, creatine phosphate, creatine and the mitochondrial oxygen consumption rate of the viable left and right ventricles of the HF animal. The improvement of the cardiac output index and high-energ y phosphate levels of the HF rat by the ACE inhibitors was associated with the recovery of the mitochondrial oxygen consumption rate. In sha m-operated animals, treatment with the ACE inhibitors reduced mean art erial pressure and left ventricular systolic pressure, but not metabol ic variables concerning myocardial energy metabolism. The present resu lts provide evidence that ACE inhibitor therapy improves cardiac funct ion and myocardial energy metabolism of experimental animals with chro nic heart failure. The mechanism underlying the benefit of long-term t reatment with ACE inhibitors is probably attributable to recovery or p reservation of the mitochondrial function and reduction in preload. (C ) 1995 Academic Press Limited