Suzuki Akihiro, Aizawa Kei, Gassmayr Susanne, Bosnjak Zeljko J, Kwok Wai-Meng
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee 53226, USA.
Anesthesiology. 2002 Nov;97(5):1209-17. doi: 10.1097/00000542-200211000-00026.
The mechanism underlying isoflurane modulation of cardiac electrophysiology is not well understood. In the present study, the authors investigated the effects of isoflurane on the cardiac action potential (AP) characteristics. The results were correlated to modulation of the L-type calcium (I(Ca,L)), the delayed-rectifier potassium (I(Kdr)), and the inward-rectifier potassium (I(Kir)) currents.
Single ventricular myocytes were enzymatically isolated from guinea pig hearts. The current clamp and whole cell voltage clamp configurations of the patch clamp technique were used to monitor the cardiac AP and ionic currents, respectively. A dynamic AP voltage protocol that mimicked changes in membrane potential during an AP was used to monitor the I(Ca,L), I(Kdr) and I(Kir).
Isoflurane produced a concentration-dependent, biphasic effect on the AP duration (APD). At 0.6 mm (1.26 vol%), isoflurane significantly increased APD50 and APD90 by 50.0 +/- 7.6% and 48.9 +/- 7.2%, respectively (P < 0.05; n = 6). At 1.0 mm (2.09 vol%), isoflurane had no significant effect on APD (n = 6). In contrast, at 1.8 mm (3.77 vol%), isoflurane decreased APD50 and APD90 by 38.3 +/- 5.4% and 32.2 +/- 5.5%, respectively (P < 0.05; n = 7). The inhibitory effects of isoflurane on I(Kdr) chord conductance were greater than those on I(Ca,L) (P < 0.05; n = 6/group). Both I(Ca,L) inactivation and I(Kdr) activation kinetics were accelerated by isoflurane. Isoflurane had no significant effects on I(Kir) chord conductance (n = 6).
At the lower anesthetic concentration, the prolongation of the APD may be the result of the dominant inhibitory effects of isoflurane on I(Kdr). At the higher concentration, the shortening of the APD may be caused by the inhibitory effects on I (Ca,L) combined with the isoflurane-induced acceleration of I(Ca,L) inactivation kinetics. Because I(Kdr) is significantly inhibited by isoflurane, I(Kir) appears to be the major repolarizing current, which is minimally affected by isoflurane.
异氟烷对心脏电生理的调节机制尚未完全明确。在本研究中，作者探究了异氟烷对心脏动作电位（AP）特征的影响。研究结果与L型钙电流（I(Ca,L)）、延迟整流钾电流（I(Kdr)）和内向整流钾电流（I(Kir)）的调节相关。
从豚鼠心脏中酶解分离出单个心室肌细胞。膜片钳技术的电流钳和全细胞电压钳模式分别用于监测心脏AP和离子电流。采用模拟AP期间膜电位变化的动态AP电压方案来监测I(Ca,L)、I(Kdr)和I(Kir)。
异氟烷对AP时程（APD）产生浓度依赖性的双相效应。在0.6 mmol/L（1.26 vol%）时，异氟烷使APD50和APD90分别显著增加50.0±7.6%和48.9±7.2%（P<0.05；n = 6）。在1.0 mmol/L（2.09 vol%）时，异氟烷对APD无显著影响（n = 6）。相比之下，在1.8 mmol/L（3.77 vol%）时，异氟烷使APD50和APD90分别降低38.3±5.4%和32.2±5.5%（P<0.05；n = 7）。异氟烷对I(Kdr)弦电导的抑制作用大于对I(Ca,L)的抑制作用（P<0.05；n = 6/组）。异氟烷加速了I(Ca,L)失活和I(Kdr)激活动力学。异氟烷对I(Kir)弦电导无显著影响（n = 6）。
在较低麻醉浓度下，APD延长可能是异氟烷对I(Kdr)的主要抑制作用所致。在较高浓度下，APD缩短可能是对I(Ca,L)的抑制作用以及异氟烷诱导的I(Ca,L)失活动力学加速共同作用的结果。由于I(Kdr)受到异氟烷的显著抑制，I(Kir)似乎是主要的复极电流，受异氟烷影响最小。
