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ANESTHETIC PHARMACOLOGY

The Effects of Sevoflurane and Propofol on QT Interval and Heterologously Expressed Human Ether-A-Go-Go Related Gene Currents in Xenopus Oocytes

Masana Yamada, MD^*, Noboru Hatakeyama, MD, PhD^*, Anna P. Malykhina, PhD, Mitsuaki Yamazaki, MD, PhD^*, Yasunori Momose, PhD, and Hamid I. Akbarali, PhD

*Department of Anesthesiology, University of Toyama, Toyama, Japan, Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; Department of Clinical Pharmacy, Toho University, Chiba, Japan

Address correspondence and reprint requests to Noboru Hatakeyama, MD, PhD, Department of Anesthesiology, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama-shi, Toyama 930–0194, Japan. Address e-mail to nobo{at}ms.toyama-mpu.ac.jp.

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.

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