Department of Anesthesiology, Shiga University of Medical Science, Otsu, Shiga, 520-2192, Japan.
Department of Physiology, Shiga University of Medical Science, Otsu, Shiga, 520-2192, Japan.
J Anesth. 2023 Oct;37(5):806-810. doi: 10.1007/s00540-023-03238-9. Epub 2023 Jul 31.
This simulation study was designed to predict the torsadogenicity of sevoflurane and propofol in healthy control, as well as type 1 and type 2 long QT syndrome (LQT1 and LQT2, respectively), using the O'Hara-Rudy dynamic model. LQT1 and LQT2 models were simulated by decreasing the conductances of slowly and rapidly activating delayed rectifier K currents (I and I, respectively) by 50%, respectively. Action potential duration at 50% repolarization level (APD) and diastolic intracellular Ca concentration were measured in epicardial cell during administration of sevoflurane (1 ~ 5%) and propofol (1 ~ 10 μM). Torsadogenicity can be predicted from the relationship between APD and diastolic intracellular Ca concentration, which is classified by the decision boundary. Whereas the relationships in control and LQT1 models were distributed on nontorsadogenic side in the presence of sevoflurane at all tested concentrations, those in LQT2 models were shifted to torsadogenic side by concentrations of ≥ 2%. In all three models, propofol shifted the relationships in a direction away from the decision boundary on nontorsadogenic side. Our findings suggest that sevoflurane, but not propofol, exerts torsadogenicity in patients with reduced I, such as LQT2 patients. Caution should be paid to the occurrence of arrhythmia during sevoflurane anesthesia in patients with reduced I.
本模拟研究旨在使用 O'Hara-Rudy 动力学模型预测七氟醚和异丙酚在健康对照者、1 型长 QT 综合征（LQT1）和 2 型长 QT 综合征（LQT2）患者中的致扭转型作用。通过分别降低缓慢激活延迟整流钾电流（I）和快速激活延迟整流钾电流（I）的电导 50%来模拟 LQT1 和 LQT2 模型。在给予七氟醚（1%5%）和异丙酚（110 μM）时，测量心外膜细胞中的动作电位复极 50%时程（APD）和舒张期细胞内 Ca 浓度。致扭转型作用可以通过 APD 和舒张期细胞内 Ca 浓度之间的关系来预测，该关系通过决策边界进行分类。虽然在所有测试浓度下，七氟醚在对照和 LQT1 模型中的关系均分布在非致扭转型侧，但在 LQT2 模型中，浓度≥2%时则转移至致扭转型侧。在所有三种模型中，异丙酚均使关系向非致扭转型侧的决策边界远离。我们的研究结果表明，七氟醚而非异丙酚可在 I 降低的患者（如 LQT2 患者）中产生致扭转型作用。在 I 降低的患者中进行七氟醚麻醉时应注意心律失常的发生。
