Preservation of cardiac function and energy reserve by the angiotensin-converting enzyme inhibitor quinapril during postmyocardial infarction remodeling in the rat

Purpose: Angiotensin-converting enzyme (ACE) inhibitors show beneficial lon gterm hemodynamic effects in chronically infarcted hearts. The purpose of t his 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-we ek old rats were randomly assigned to ligation of the left coronary artery [mycardial infarction (MI)] or sham operation (Sham) and to the ACE inhibit or quinapril (+Q) (6 mg/kg/day per gavage) or placebo treatment. Eight week s later, cardiac function was measured in the isolated heart by a left vent ricular balloon (pressure-volume curves), and energy metabolism of residual intact myocardium was analyzed in terms of total and isoenzyme creatine ki nase activity (spectrophotometry), steady-state levels [adenosine triptosph ate (ATP), phosphocreatine], and turnover rates (creatine kinase reaction v elocity) of high-energy phosphates [P-31 nuclear magnetic resonance (NMR)] and total creatine content [high-performance liquid chromatography (HPLC)]. Results: Quinapril prevented post-MI hypertrophy and partially prevented l eft 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 MI+Q hearts]. Resi dual intact failing myocardium showed a 17% decrease of MM-CK and a 16% dec rease of mito-CK activity. Total creatine was reduced by 23%, phosphocreati ne by 26% and CK reaction velocity by 30%. Parallel to improved function, t reatment with quinapril largely prevented the impairment of energy metaboli sm occuring post-MI. Conclusions: quinapril treatment results in an improve ment of high-energy phosphate metabolism, of energy reserve via the creatin e kinase reaction, and of contractile performance post-MI.