Depressed tolerance to fluorocarbon-simulated ischemia in failing myocardium due to impaired [Ca2+](i) modulation

The aim of this study was to investigate the tolerance of failing myocardiu m from postinfarction rats to simulated ischemia. Myocardial infarction (NI ) was induced by ligation of the left coronary artery in male Wistar rats. Isometric force and free intracellular Ca2+ concentration ([Ca2+](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 flu orocarbon immersion with hypoxia. Results showed that mechanical performanc e 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 [Ca2+](i) (hypox ia: 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 = N S). After reoxygenation, [Ca2+](i) rapidly returned to near preischemic bas al levels, whereas developed tension in fluorocarbon remained significantly lower. This dissociation between peak [Ca2+](i) and isometric contractilit y was more pronounced in the failing myocardium from postinfarction rats. I n conclusion, more severe impairment of [Ca2+](i) homeostasis in the failin g myocardium from postinfarction rats increases susceptibility to ischemia- reperfusion injury.