Halothane Depression of Myocardial Slow Action Potentials

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Effects of halothane on myocardial electrophysiologic and contractile properties were studied by simultaneous measurement of action potentials (APs) and contractions in guinea pig papillary muscle. Muscles were stimulated by field electrodes and normal responses measured before, during, and after recovery from halothane application. Halothane was administered in 0.5 per cent to 4 per cent concentrations in 5 per cent CO2–95 per cent O2 bubbled through standard Tyrode perfusing solutions. Slow action potentials were then induced with 10−7 isoproterenol in partially depolarized muscles (typically −40 mV in 26 mM K+ media). AP characteristics and accompanying contractions were again measured before, during, and after halothane application.The maximum rate of rise (+max) of the normal (fast) AP was not depressed in any concentration of halothane, although amplitude and duration were decreased in 3 per cent halothane. In contrast, halothane depressed +max of the slow AP to 61 per cent, 28 per cent, and 14 per cent of control, in concentrations of 1, 2 and 3%, respectively. Decreased duration and decreased amplitude (85% of control of the slow AP), or loss of excitability (4 of 7 muscles) occurred in 3 per cent halothane. Initially, halothane application caused a 5 per cent enhancement of tension with both fast and slow APs. In 0.5 per cent halothane, contractions subsequently declined to steady-state levels of 66 per cent (fast AP) and 76 per cent (slow AP) of control. Contractions were depressed linearly with log dose to 18 per cent (fast AP) and 5 per cent (slow AP) of control in 3 per cent halothane.Halothane concentrations of 1 per cent and greater inhibit slow (Na+ – Ca++) channels which mediate the slow action potentials. The negative inotropic effect of halothane may be due in part to decreased Ca++ influx through the slow channel. The negative inotropic effect of 0.5 per cent halothane, in which the slow AP is unaffected, suggests that additional mechanisms, not involving the slow channel, also participate in the negative inotropic action of halothane.

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