Näbauer M, Kääb S
Department of Medicine I, University of München, Klinikum Grosshadern, Germany.
Cardiovasc Res. 1998 Feb;37(2):324-34. doi: 10.1016/s0008-6363(97)00274-5.
Prolongation of action potential duration is the most consistent electrophysiological abnormality in myocardium and myocytes from hypertrophied and failing hearts. Measurements of currents in myocytes from hypertrophied and failing hearts indicate that, in most cases, this is due to a decrease in outward potassium currents. If present, a calcium-independent transient outward current is usually substantially reduced, but delayed rectifier and inward rectifier currents have also been found to be diminished. There is increasing evidence that potassium current down-regulation contributes significantly to the enhanced lability of the repolarization process in heart failure, predisposing to early after-depolarizations, dispersion of repolarization and ventricular arrhythmias. The reduction of outward potassium currents may also be involved in the enhanced sensitivity of failing myocardium to triggering factors like hypokalemia, ischemia, and antiarrhythmic agents with Class III effects. A thorough understanding of the mechanisms of cardiac excitability and arrhythmogenesis at the cellular and molecular level under normal and pathological conditions will be essential for the development of new pharmacological strategies to prevent sudden cardiac death in heart failure.
动作电位时程延长是肥厚性和衰竭心脏的心肌及心肌细胞中最一致的电生理异常。对肥厚性和衰竭心脏的心肌细胞电流测量表明，在大多数情况下，这是由于外向钾电流减少所致。如果存在，与钙无关的瞬时外向电流通常会大幅降低，但延迟整流电流和内向整流电流也被发现有所减少。越来越多的证据表明，钾电流下调在心力衰竭时复极化过程的易损性增强中起重要作用，易引发早期后去极化、复极化离散和室性心律失常。外向钾电流的减少也可能与衰竭心肌对低钾血症、缺血和具有Ⅲ类效应的抗心律失常药物等触发因素的敏感性增强有关。在正常和病理条件下，从细胞和分子水平深入了解心脏兴奋性和心律失常发生机制，对于开发预防心力衰竭心脏性猝死的新药理学策略至关重要。
