Depressed tolerance to fluorocarbon-simulated ischemia in failing myocardium due to impaired [Ca(2+)](i) modulation.
The aim of this study was to investigate the tolerance of failing myocardium from postinfarction rats to simulated ischemia. Myocardial infarction (MI) was induced by ligation of the left coronary artery in male Wistar rats. Isometric force and free intracellular Ca(2+) concentration ([Ca(2+)](i)) were measured in isolated left ventricular papillary muscles from sham-operated and post-MI animals 6 wk after surgery. Ischemia was simulated by using fluorocarbon immersion with hypoxia. Results showed that mechanical performance was depressed during the period of hypoxia in physiological salt solution (44 +/- 7% of baseline in sham vs. 30 +/- 6% of baseline in MI, P < 0.05) or ischemia (16 +/- 2% of baseline in sham vs. 9 +/- 1% of baseline in MI, P < 0.01) accompanied by no corresponding decrease of peak [Ca(2+)](i) (hypoxia: 51 +/- 8% of baseline in sham vs. 46 +/- 7% of baseline in MI, P = NS; ischemia: 47 +/- 5% of baseline in sham, 39 +/- 7% of baseline in MI, P = NS). After reoxygenation, [Ca(2+)](i) rapidly returned to near preischemic basal levels, whereas developed tension in fluorocarbon remained significantly lower. This dissociation between peak [Ca(2+)](i) and isometric contractility was more pronounced in the failing myocardium from postinfarction rats. In conclusion, more severe impairment of [Ca(2+)](i) homeostasis in the failing myocardium from postinfarction rats increases susceptibility to ischemia-reperfusion injury.
Min
J Y
JY
Charles A. Dana Research Institute and the Harvard-Thorndike Laboratory, Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachussetts 02215, USA.
Hampton
T G
TG
Wang
J F
JF
DeAngelis
J
J
Morgan
J P
JP
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D003331:Coronary Vessels / Q000502:physiology / Q000601:surgery; D005466:Fluorocarbons; D006352:Heart Ventricles / Q000378:metabolism; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D007537:Isometric Contraction / Q000187:drug effects / Q000502:physiology; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000139:chemically induced / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism / Q000494:pharmacology; D010210:Papillary Muscles / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D005466:Fluorocarbons; D010100:Oxygen; D002118:Calcium