Reduction in the myocardial sodium current by halothane and thiamylal.

Abstract

Effects of two general anesthetics, halothane and thiamylal, on the fast sodium inward current (INa) of enzymatically isolated single rat ventricular cells were studied under current clamp and voltage clamp conditions. A suction pipette technique was used for potential measurement, current injection and internal perfusion of isolated cells. In current clamp experiments, sodium action potential was elicited in a Ca-free Co Krebs solution and the action potential was reduced by 0.5°c halothane and 5 x 10-5 M thiamylal. In voltage clamp experiments, the calcium current was suppressed by replacing Ca with Co and the potassium current was eliminated by replacing K with Cs and adding 4-aminopyridine and tetraethylammonium. Both anesthetics decreased INa, in a dose dependent manner, without changing the shape of the current-voltage curve. Halothane (l°) shifted the steady state inactivation curve in a negative direction along the potential axis by 8.5±2 mV (mean + S.D., n=4). Thiamylal, 5 x 10-5 and 10-4M, shifted the curve in a negative direction by 4.4 ± 0.8 mV (n =5) and 8.6 + 3.2 mV (n = 5), respectively. Both agents slightly reduced the maximum sodium conductance (gNa). Halothane (1 %) increased half recovery time from inactivation measured at -80 mV from 30±15 to 80 + 25 ms (n=4). Thiamylal (104M) -prolonged it at -75 mV from 50± 20 to 110± 15 ms (n=5). With a test pulse duration of 50 ms, neither drug produced a use-dependent inhibition of INa. Halothane and thiamylal depress the INa of cardiac muscles mainly by shifting the steady state inactivation curve in a negative direction along the potential axis. Relatively small prolongation of half recovery time from inactivation and no sign of use-dependent inhibition suggest a molecular mechanism which differs in some respects from the local anesthetics.

Electrophysiologic effects of volatile anesthetics, sevoflurane and halothane, in a canine myocardial infarction model

“…Halothane showed only a slight effect on the activation of the normal zone, which was consistent with a previous report that halothane did not depress the Vmax of Purkinje fibers in non-infarcted zones [8]. According to Ikemoto et al [17], halothane depresses the sodium currents of cardiac muscles, and shifts the steady state inactivation curve in a negative direction along the potential axis. Thus, the effect of halothane on delayed activation may be caused by an inhibition of sodium channels.…”

Halothane inhibits two components of calcium current in clonal (GH3) pituitary cells

“…The underlying mechanism of volatile anesthetic action presumably involves alteration of one or more membrane conductances, though as yet there has been little success in attempting to correlate anesthetic action with effects on any specific membrane current. For example, halothane has been shown to reduce Na+ current both in neuronal (Bean et al, 1981;Haydon and Urban, 1983) and in a number of non-neuronal preparations (heart muscle: Ikemoto et al, 1986;skeletal muscle: Ruppersberg and Rudel, 1988). However, the reduction of Na+ current by halothane occurs at clinically unreasonable concentrations.…”

Electrophysiologic Interaction between Class I Antiarrhythmic Drugs and Volatile Anesthetics in Depressant Effects on Ventricular Activation in a Canine Myocardial Infarction Model

“…According to Turner et al, halothane decreases the Vma, in the isolated Purkinje fibers of the infarcted zone, whereas it does not decrease the Vmax in the non-infarcted zones (5). Ikemoto et al reported that halothane depresses the sodium cur rents of cardiac muscles and shifts the steady state inacti vation curve in a negative direction along the potential axis (17). Sevoflurane and isoflurane may have similar effects, which may cause a selective depression of delayed conduction in the infarcted zone.…”

“…Sevoflurane and isoflurane may have similar effects, which may cause a selective depression of delayed conduction in the infarcted zone. However, several inves tigators suggested that mechanisms of the effects of the volatile anesthetics and class I antiarrhythmic drugs on ventricular conduction may be different (10,17,18). Ozaki et al reported that halothane and enflurane depressed the conduction velocity without depressing vmax in isolated guinea pig papillary muscle (10).…”