title: Preservation of left ventricular mechanical function and energy metabolism in rats after myocardial infarction by the angiotensin-converting enzyme inhibitor quinapril.
abstract: We tested whether angiotensin-converting enzyme (ACE) inhibitor therapy with quinapril prevents the deterioration of mechanical function and high-energy phosphate metabolism that occurs in chronically infarcted heart. Rats were subjected to ligation of the left anterior descending coronary artery (LAD) or sham operation. Four groups were studied: sham-operated rats (n = 10), rats with myocardial infarction (MI, n = 9), sham-operated quinapril-treated rats (n = 8), and infarcted quinapril-treated (n = 13) rats. Treated rats received 6 mg/kg/day of the ACE inhibitor quinapril orally, initiated 1 h after MI or sham operation. Eight weeks after LAD ligation or sham operation, hearts were isolated and buffer-perfused isovolumically. High-energy phosphate metabolism and intracellular pH were continuously recorded with 31P-nuclear magnetic resonance (NMR) spectroscopy. Hearts were subjected to 15-min control, 30-min hypoxia (95% N2/5% CO2, and 30-min reoxygenation. Left ventricular developed pressure (LVDP) was reduced in infarcted hearts (58 +/- 10 vs. 98 +/- 9 mm Hg in sham, p < 0.05), and this reduction was partially prevented by quinapril (78 +/- 8 mm Hg). ATP content of residual intact myocardium after sham operation or MI was unchanged. Creatine phosphate was reduced in infarcted hearts (107 +/- 10 vs. 138 +/- 5% of control ATP, p < 0.05), and quinapril prevented this decrease (131 +/- 8%). Therefore, quinapril preserved both function and high-energy phosphate metabolism in the chronically infarcted heart. However, when hearts were subjected to acute hypoxia, susceptibility to acute metabolic stress was substantially increased in both quinapril-treated groups: ATP content at end-hypoxia was reduced to 31 +/- 7 and 37 +/- 6% in sham and infarcted quinapril-treated groups, whereas ATP in untreated sham and infarcted hearts was 66 +/- 6 and 66 +/- 3% of baseline values (p < 0.05 untreated vs. quinapril treated). Likewise, recovery of LVDP during reoxygenation was impaired by quinapril treatment (15 +/- 7 and 15 +/- 4 mm Hg in quinapril-treated sham and MI vs. 73 +/- 9 and 46 +/- 9 mm Hg in untreated sham and MI groups, p < 0.05 untreated vs. quinapril treated). The most likely explanation for the unexpected finding of increased susceptibility to acute metabolic stress in the quinapril-treated groups is reduced wall thickness leading to increased wall stress. The preservation of high-energy phosphate content in residual intact hearts after MI may contribute to the beneficial effects of ACE inhibitors after MI.
authors.affiliation: Medizinische Universitatsklinik, Wurzburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Horn
authors.forename: S
authors.initials: S
authors.lastname: Neubauer
authors.forename: S
authors.initials: S
authors.lastname: Frantz
authors.forename: S
authors.initials: S
authors.lastname: Hugel
authors.forename: K
authors.initials: K
authors.lastname: Hu
authors.forename: P
authors.initials: P
authors.lastname: Gaudron
authors.forename: K
authors.initials: K
authors.lastname: Schnackerz
authors.forename: G
authors.initials: G
authors.lastname: Ertl
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D004734:Energy Metabolism / Q000187:drug effects*; D000860:Hypoxia / Q000139:chemically induced / Q000378:metabolism; D007546:Isoquinolines / Q000009:adverse effects / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D010710:Phosphates / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism*; D000077583:Quinapril; D051381:Rats; D017208:Rats, Wistar; D044005:Tetrahydroisoquinolines; D018487:Ventricular Dysfunction, Left / Q000378:metabolism / Q000517:prevention & control*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D007546:Isoquinolines; D010710:Phosphates; D044005:Tetrahydroisoquinolines; D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D000077583:Quinapril