Remodeling in the Rat

Purpose: Angiotensin-converting enzyme (ACE) inhibitors show beneficial long-term hemodynamic effects in chronically infarcted hearts. The purpose of this study was to test whether prevention of the deterioration of mechanical function by ACE inhibitors is related to beneficial effects on high-energy phosphate metabolism that is deranged in heart failure. Methods: Twelve-week old rats were randomly as-signed to ligation of the left coronary artery [mycardial infarction (MI)] or sham operation (Sham) and to the ACE inhibitor quinapril (Q) (6 mg/kg/day per ga-vage) or placebo treatment. Eight weeks later, cardiac function was measured in the isolated heart by a left ventricular balloon (pressure-volume curves), and energy metabolism of residual intact myocardium was analyzed in terms of total and isoen-zyme creatine kinase activity (spectrophotometry), steady-state levels [adenosine triptosphate (ATP), phosphocreatine], and turnover rates (creatine kinase reaction velocity) of high-energy phosphates [31P nuclear magnetic resonance (NMR)] and total creatine content [high-performance liquid chromatography (HPLC)]. Results: Quinapril prevented post-MI hypertrophy and partially prevented left ventricular contractile dysfunction [maximum left ventricular developed pressure 166 6, 83 16 (p 0.05 MI vs. Sham), 139 13 mm Hg (p 0.05 quinapril treated vs. untreated) in Sham, MI and MIQ hearts]. Residual intact failing myocardium showed a 17 % decrease of MM-CK and a 16 % decrease of mito-CK activity. Total Address correspondence and reprint requests to Stephanie Hügel