[Mechanism of QT interval prolongation induced by sevoflurane in guinea-pig ventricular myocyte].
BACKGROUND
Sevoflurane causes QT interval prolongation clinically, but its precise mechanism has not been clarified. We examined the mechanism of QT interval prolongation induced by sevoflurane by means of electrophysiological technique in guinea-pig ventricular myocyte.


METHODS
Electrocardiogram was recorded in guinea-pig and effect of sevoflurane (1, 2, 4%) was examined. Action potential (AP), delayed rectified potassium current (IKr), and L-type calcium channel current (ICa) were monitored as whole-cell current and by voltage clamp techniques in guinea-pig single ventricular myocytes. Sevoflurane was applied by bubbling into the bathing solution.


RESULTS
Sevoflurane (1, 2, 4%) increased QTc value. Sevoflurane prolonged the duration of AP at 2%, but shortened it at 6%. IKr was reduced to 35% of control in the presence of 2% sevoflurane, but a higher concentration (6%) did not show further inhibition. ICa was reduced only to 87% of control in the presence of 2% sevoflurane and the reduction was dose-dependent (4, 6%).


CONCLUSIONS
Sevoflurane 2% inhibited IKr, but it showed only slight inhibition on ICa. Because the duration of AP is regulated by ICa (plateau phase) and IKr (repolarization), greater inhibition of IKr than ICa could result in prolongation of AP. It is suggested that this mechanism may play a role in QT interval prolongation under sevoflurane anesthesia.
Yamada
Masana
M
Department of Anesthesiology, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Toyama 930-0194.
Hatakeyama
Noboru
N
Shibuya
Nobuko
N
Momose
Yasunori
Y
Yamazaki
Mitsuaki
M
D000200:Action Potentials; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D015220:Calcium Channels / Q000502:physiology; D004562:Electrocardiography; D005260:Female; D006168:Guinea Pigs; D008133:Long QT Syndrome / Q000139:chemically induced*; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology; D000077149:Sevoflurane
D018685:Anesthetics, Inhalation; D015220:Calcium Channels; D008738:Methyl Ethers; D000077149:Sevoflurane