Cardiac Electrophysiology in Anesthetic-Induced Preconditioning

项目III的总体目标是研究挥发性麻醉剂和麻醉诱导预处理（APC）对心脏电生理影响的离子机制。APC模拟缺血预处理（IPC），通过减少梗死面积来量化，但它是否也在心肌缺血和再灌注期间提供心律失常保护尚不清楚。in项目提出的实验将使用Langendorff离体心脏方法表征APC大鼠的心律，并使用膜片钳技术研究潜在的离子机制。尽管肌层KATPchannel的激活，假设发生在APC期间，可以深刻地影响心脏

The overall goal of Project III is to investigate the ionic mechanisms underlying the effects of volatile anesthetics and anesthetic-induced preconditioning (APC) on cardiac electrophysiology. APC mimics ischemic preconditioning (IPC) as quantified by reduction in infarct size, but whether it also provides protection from cardiac arrhythmias during myocardial ischemia and reperfusion is not well established. The experiments proposed in Project In will characterize cardiac rhythm in APC rats using the Langendorff isolated heart methodology, and investigate the underlying ionic mechanisms using the patch clamp technique. Though activation of the sarcolemmal KATPchannel, hypothesized to occur during APC, can profoundly affect cardiac electrophysiology, the intracellular signaling pathways thought to mediate APC, for example, PKC (protein kinase C), PTK (protein tyrosine kinase), and MAPK (mitogen-activated protein kinase) pathways, also modulate the voltage-gated channels. The key question is whether these changes in signal transduction have a "delayed" effect on the ion channels to coincide with the time course of APC. The general hypothesis to be tested in this proposal is that volatile anesthetics produce cardioprotective antiarrhythmic effects by facilitating the actions of the kinase-dependent pathways potentiated or triggered by APC on the voltage-gated ion channels, specifically the fast Na, L-type Ca and transient outward K channels. This will be tested by utilizing rats post-APC and various genetic strains of rats with differential sensitivity to APC. The following aims and hypotheses will be pursued: Aim I: To characterize the effects of APC on cardiac rhythm using the Langendorff isolated heart. Aim II: To characterize the effects of volatile anesthetics on the cardiac action potential in ventricular myocytes isolated from normal and APC rat hearts. Aim III: To characterize the modulation of I(Na), I(Ca),L and I(to) in ventricular myocytes isolated from normal and APC rat hearts. Functional protection, particularly with regard to suppression of arrhythmias associated with myocardial ischemia and reperfusion, has yet to be clearly established. The experiments designed in this proposal will characterize the role of ion channels other than the sarcolemmal K(ATP) channel in contributing to the antiarrhythmic effects of APC.