Background: Recent experimental data suggest that functional and metabolic changes in the myocardium caused during ischemia and subsequent reperfusion may be attenuated by the volatile anesthetics through the prevention of intracellular calcium accumulation. The main purpose of the current research is to identify a mechanism responsible for the alterations of ischemia-associated injury to the voltage-sensitive Ca2+ channels (VSCC) in the sarcolemma during halothane anesthesia.
Methods: The effect of 10 min myocardial ischemia in canine heart and 20 min reperfusion on the function of the VSCC in the sarcolemma was examined in the presence or absence of 1.6 vol% halothane administered in vivo. The membranes were isolated through differential centrifugation/filtration from the ischemic (left anterior descending territory) and normally perfused myocardium. Comparison of binding characteristics in the ischemic and nonischemic zones was made using equilibrium-binding studies of a dihydropyridine calcium channel blocker, [3H]isradipine (0.05-1.0 nM), to the VSCC in the sarcolemma. Control studies were performed on membranes prepared from the same perfusion zones, but from hearts who were not exposed to ischemia.
Results: The control studies (n = 5) showed no difference in binding kinetics between the different zones in the heart. After 10 min of ischemia, a 50 to 95% increase in specific [3H]isradipine binding to the sarcolemmal membranes was observed as compared to control membranes (P < 0.001). The maximal binding capacity (Bmax) increased by 85%, whereas the dissociation constant (Kd) remained unchanged. In the reperfusion experiments, a moderately increased binding (of 32%) was observed with a 40% increase in Bmax (P = NS). In the presence of 1.6% inhaled halothane, the effect of ischemia was attenuated. A decrease of 32.1% to 41.8% in equilibrium binding was observed (31% decrease in Bmax; P < 0.03 and 0.02, respectively).
Conclusions: Even a brief period of myocardial ischemia produces a marked increase in the available high-affinity binding sites in the VSCC, a finding that is well correlated with previous experimental observation of increased calcium ion influx to the myocardial cell. On reperfusion, some recovery of the ischemic changes in the VSCC was evident. The binding kinetics which characterize this early phase of cell injury were reversed by halothane anesthesia, indicating a possible reduction in calcium entry, which may represent one of the beneficial effects of the anesthetic in the ischemic heart.