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 treatment may enhance tolerance to ischemia in normal and postinfarction rat myocardium. Myocardial infarction was induced by permanent ligation of the left coronary artery in adult rats. Animals were divided into sham-operated and infarction groups with or without metoprolol treatment. Metoprolol treatment (60 mg/kg/day via gastric gavage) was started on the second day after surgery and continued until sacrifice at 6 weeks after myocardial infarction. Isometric force and intracellular Ca(2+) ([Ca(2+)](i)) transients were simultaneously recorded in isolated left ventricular papillary muscles. Ischemia was simulated by immersing the muscles into fluorocarbon with hypoxia. Metoprolol treatment induced a significant improvement of isometric force and ameliorated diastolic [Ca(2+)](i) overload in postinfarction rat myocardium at baseline. Metoprolol treatment also reduced diastolic [Ca(2+)](i), ameliorated the depression of developed tension during ischemia, and enhanced recovery of postischemic depressed myocardial function in sham-operated and postinfarction rat papillary muscles. Protein levels of the sarcoplasmic reticulum Ca(2+) ATPase of left ventricles and postischemic papillary muscles from metoprolol-treated rats were higher than those in placebo-treated animals. We concluded, therefore, that metoprolol treatment produced appreciable improvement of intracellular Ca(2+) handling during ischemia-reoxygenation cycles, and enhanced recovery of postischemic depressed myocardial function in both normal and postinfarction rat myocardium.
Min
J Y
JY
The Charles A. Dana Research Institute and the Harvard-Thorndike Laboratory, Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA.
Ding
B
B
Wang
J F
JF
Sullivan
M F
MF
Morgan
J P
JP
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000187:drug effects / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000187:drug effects / Q000378:metabolism; D005466:Fluorocarbons / Q000494:pharmacology; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D008790:Metoprolol / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D009203:Myocardial Infarction / Q000503:physiopathology*; D017202:Myocardial Ischemia / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D010100:Oxygen / Q000494:pharmacology; D010210:Papillary Muscles / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000099211:Phospholamban
D000319:Adrenergic beta-Antagonists; D002118:Calcium; D002135:Calcium-Binding Proteins; D000252:Calcium-Transporting ATPases; D005466:Fluorocarbons; D008790:Metoprolol; D010100:Oxygen; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000099211:Phospholamban