Stowe David F, Kevin Leo G
Anesthesiology Research Laboratories, Department of Anesthesiology, and Cardiovascular Research Center, The Medical College of Wisconsin, Milwaukee, WI, USA.
Antioxid Redox Signal. 2004 Apr;6(2):439-48. doi: 10.1089/152308604322899512.
Volatile anesthetic agents, such as halothane, isoflurane, and sevoflurane, are the drugs most commonly used to maintain the state of general anesthesia. They have long been known to provide some protection against the effects of cardiac ischemia and reperfusion. Several mechanisms likely contribute to this cardioprotection, including coronary vasodilation, reduced contractility with corresponding decreased metabolic demand, and a direct effect to decrease myocardial Ca(2+) entry through L-type Ca(2+) channels. Recently, a memory phase to cardioprotection has been observed by these agents, which is inhibited by ATP-sensitive potassium channel inhibition. These features suggest a pathway that shares components with those required for ischemic preconditioning, despite the remarkable differences between these two stimuli, and the term anesthetic preconditioning (APC) has been adopted. Scavengers of reactive oxygen species (ROS) abrogate APC, suggesting an effect of anesthetic agents to cause ROS formation. Such an effect has recently been directly demonstrated. The mechanism by which these drugs induce ROS formation is unclear. However, direct inhibition of mitochondrial electron transport system enzymes, and altered mitochondrial bioeneregtics in hearts preconditioned by volatile anesthetics, strongly implicate the mitochondria as the target for these effects. Furthermore, decreased mitochondrial ROS formation during ischemia and reperfusion in hearts preconditioned by volatile anesthetics might underlie the improved postischemic structure and function. APC presents a safe mode to apply preconditioning to human hearts. This review summarizes the major developments in a field that is exciting to clinicians and basic scientists alike.
挥发性麻醉剂，如氟烷、异氟烷和七氟烷，是最常用于维持全身麻醉状态的药物。长期以来，人们已知它们能对心脏缺血和再灌注的影响提供一定保护。几种机制可能促成了这种心脏保护作用，包括冠状动脉血管舒张、收缩力降低以及相应的代谢需求减少，以及通过L型钙通道减少心肌钙内流的直接作用。最近，这些药物观察到了心脏保护的记忆阶段，该阶段可被ATP敏感性钾通道抑制所阻断。这些特征表明存在一条与缺血预处理所需途径有共同成分的通路，尽管这两种刺激之间存在显著差异，“麻醉预处理（APC）”这一术语已被采用。活性氧（ROS）清除剂可消除APC，这表明麻醉剂有导致ROS形成的作用。最近已直接证明了这种作用。这些药物诱导ROS形成的机制尚不清楚。然而，直接抑制线粒体电子传递系统酶，以及挥发性麻醉剂预处理的心脏中线粒体生物能量学的改变，强烈表明线粒体是这些作用的靶点。此外，挥发性麻醉剂预处理的心脏在缺血和再灌注期间线粒体ROS形成减少，可能是缺血后结构和功能改善的基础。APC为将预处理应用于人类心脏提供了一种安全模式。这篇综述总结了一个令临床医生和基础科学家都兴奋的领域的主要进展。
