Research on the mechanism of arrhythmia induced by general anesthetic on atrial pacemaker

全身麻醉药可通过延长动作电位持续时间引起心律失常。推测这种动作电位的延长是由于动作电位复极化相的抑制。由于人类HERG通道在此机制中起主要作用，因此本项目旨在阐明全身麻醉剂对HERG通道的影响及其起搏机制。用cRNA注入爪蟾卵母细胞表达HERG通道，七氟醚存在时，心电图QT间期延长，而丙泊酚不在临床相关范围内。七氟醚对延迟整流钾通道电流和HERG通道电流均有明显的抑制作用。七氟醚对尾HERG电流的影响大于对稳态电流的影响，由于七氟醚对复极化电流的强烈抑制，可能影响起搏机制，导致全麻时心律失常。

General anesthetics can cause arrhythmia by extending the duration of action potential. And it is supposed that this prolongation of action potential is due to the inhibition of repolarization phase of action potential. Because human ether-a-go-go related gene (HERG) channel plays major role for this mechanism, this project was carried out to clarify the effect of general anesthetic on HERG channel and pacemaking mechanism. HERG channel was expressed by injecting cRNA into Xenopus OocytesIn the presence of sevoflurane, QT interval of ECG was prolonged, where as propofol did not within clinically relevant range. Sevoflurane showed dominat inhibitory effect on both of delayed rectified potassium channel current and HERG channel current. Sevoflurane was effective more on the tail HERG current than steady state current.Because sevoflurane strongly inhibited the repolarizing currents, it could affect pacemaking mechanism and it could cause arrhythmia during general anesthesia.