Sevoflurane (1%-4%) dose-dependently prolonged QTc (7.5%-21.2%) and inhibited HERG outward tail currents (9.7%-26.6%), whereas propofol had no effect at clinically relevant concentrations.
Does sevoflurane or propofol affect QT interval and HERG currents in guinea pigs and Xenopus oocytes?
Sevoflurane, unlike propofol, prolongs the QT interval by inhibiting HERG outward tail currents, highlighting a potential proarrhythmic mechanism of the anesthetic.
Sevoflurane can induce prolongation of the cardiac QT interval by inhibiting the repolarization phase of the action potential. This may occur as a result of inhibition of the human ether-a-go-go related gene (HERG) channel. To clarify the mechanisms of anesthetics on HERG channels, we monitored the electrocardiogram and measured QT intervals in the guinea pig in the presence of sevoflurane and propofol. Sevoflurane (1%-4%) prolonged QTc dose-dependently (7.5%-21.2%), but propofol did not affect it. Furthermore, HERG channels were expressed in Xenopus oocytes and outward HERG currents were obtained on step depolarization from a holding potential of -70 mV. Repolarization to -70 mV from positive test potentials resulted in large outward tail currents. Sevoflurane (1%-4%), in a dose-dependent manner, inhibited the HERG outward tail currents (9.7%-26.6%), whereas steady-state currents were inhibited only at large concentrations. The time constant of the converging current was decreased in the presence of sevoflurane, but the inactivation and activation curves were not shifted. Propofol did not affect these currents within the clinically relevant concentration. In conclusion, compared with steady-state currents, sevoflurane was more potent in inhibiting the outward tail currents, suggesting that sevoflurane may modulate the HERG channel kinetics in its inactivated state.
Yamada et al. (Wed,) reported a other. Sevoflurane vs. Propofol was evaluated on QTc interval prolongation and HERG outward tail currents inhibition. Sevoflurane (1%-4%) dose-dependently prolonged QTc (7.5%-21.2%) and inhibited HERG outward tail currents (9.7%-26.6%), whereas propofol had no effect at clinically relevant concentrations.