Metoprolol attenuates postischemic depressed myocardial function in papillary muscles isolated from normal and postinfarction rat hearts

The present study was designed to test the hypothesis that metoprolol treat ment may enhance tolerance to ischemia in normal and postinfarction rat myo cardium. Myocardial infarction was induced by permanent ligation of the lef t coronary artery in adult rats. Animals were divided into sham-operated an d infarction groups with or without metoprolol treatment. Meroprolol treatm ent (60 mg/kg/day via gastric gavage) was started on the second day after s urgery and continued until sacrifice at 6 weeks after myocardial infarction . Isometric force and intracellular Ca2+ ([Ca2+](i)) transients were simult aneously recorded in isolated left ventricular papillary muscles. Ischemia was simulated by immersing the muscles into fluorocarbon with hypoxia. Meto prolol treatment induced a significant improvement of isometric force and a meliorated diastolic [Ca2+](i) overload in postinfarction rat myocardium at baseline. Metoprolol treatment also reduced diastolic [Ca2+](i), ameliorat ed the depression of developed tension during ischemia, and enhanced recove ry of postischemic depressed myocardial function in sham-operated and posti nfarction rat papillary muscles. Protein levels of the sarcoplasmic reticul um Ca2+ ATPase of left ventricles and postischemic papillary muscles from m etoprolol-treated rats were higher than those in placebo-treated animals. W e concluded, therefore, that metoprolol treatment produced appreciable impr ovement of intracellular Ca2+ handling during ischemia-reoxygenation cycles , and enhanced recovery of postischemic depressed myocardial function in bo th normal and postinfarction rat myocardium. (C) 2001 Published by Elsevier Science B.V.