Hemodynamic Interactions of Anesthetics and K Channel Openers in Chronically Instrumented Dogs

本研究旨在确定长期麻醉犬的KATP通道开放剂和麻醉药的血流动力学相互作用。长期测量狗的平均动脉压（MAP）、心率（HR）、左旋冠状动脉血流量（CBF）、心输出量（CO）和区域收缩功能（%SS）。在清醒状态和麻醉状态下连续测量血流动力学。KATP通道开放剂cromakalim， nicorandil和JTV-506被证明对冠状动脉舒张有选择性的有效作用。异氟醚和七氟醚引起的冠状动脉血管舒张作用被更接近KATP通道的格列本脲完全消除，提示KATP通道的活性可能是挥发性麻醉剂血管舒张作用的机制之一。异氟醚增强了cromakalim对全身和冠状血管的血管扩张作用，减弱了cromakalim引起的CO和心肌收缩力的增加。结果还提示，在动物实验中研究KATP通道打开剂的药理作用时，应排除麻醉剂的影响。心律失常实验表明，Ito通道而非KATP通道可能参与了卤烷-肾上腺素心律失常的发生机制。

The present study was carried out to determine the hemodynamic interactions of KATP channel openers and anesthetics in chronically instrumented dogs.Dogs were chronically instrumented to measure mean arterial pressure (MAP), heart rate (HR), left circumflex coronary blood flow (CBF), cardiac output (CO), and regional contractile function (%SS). Hemodynamics were measured continuously in the conscious state or during anesthesia.The KATP channel openers, cromakalim, nicorandil and JTV-506, were shown to have selectively potent effect on coronary vasodilation. The effects of coronary vasodilation caused by isoflurane and sevoflurane were completely abolished by a KATP channel closer, glibenclamide, suggesting that the activity of KATP channels might contribute the mechanism underlying volatile anesthetics on vasodilation. Isoflurane enhances the vasodilating action of cromakalim on both systemic and coronary vasculature and attenuates the cromakalim-induced increases in CO and myocardial contractility. The results also suggest that when the pharmacology of KATP channel openers are studied in animals, the effect of anesthetics should be excluded. The experiment of arrhythmias indicated that Ito but not KATP channels might be involved in the mechanism in producing halothane-epinephrine arrhythmias.