Mechanisms of altered excitation-contraction coupling in canine tachycardia-induced heart failure, I -: Experimental studies
Mechanisms of altered excitation-contraction coupling in canine tachycardia-induced heart failure, I -: Experimental studies
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DOI：
10.1161/01.res.84.5.562
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发表时间：
1999-03-19
影响因子：
20.1
通讯作者：
Marbán, E
中科院分区：
文献类型：
--
作者：
O'Rourke, B;Kass, DA;Marbán, E
起搏诱导的犬心力衰竭概括了人类疾病的许多电生理和血流动力学异常；然而，在这个模型中，改变钙离子处理的机制尚未被研究。我们现在发现，快速起搏3-4周的犬左室心肌中层细胞动作电位和钙瞬变时间延长，峰值降低，但持续时间约为对照组的3倍。为了区分动作电位对钙离子动力学的影响和钙离子调节过程的直接变化，采用电压钳方法测定了细胞内钙离子清除的时间常数(tau(Ca))。在生理溶液中固定电压阶跃后，衰竭心脏的心肌细胞tau钙仅延长35%(tau(Ca)对照组，216+/-25ms，n=17；tau(Ca)衰竭，292+/-23ms，n=22；P
Pacing-induced heart failure in the dog recapitulates many of the electrophysiological and hemodynamic abnormalities of the human disease; however, the mechanisms underlying altered Ca2+ handling have not been investigated in this model. We now show that left ventricular midmyocardial myocytes isolated from dogs subjected to 3 to 4 weeks of rapid pacing have prolonged action potentials and Ca2+ transients with reduced peaks, but durations approximate to 3-fold longer than controls. To discriminate between action potential effects an Ca2+ kinetics and direct changes in Ca2+ regulatory processes, voltage-clamp steps were used to examine the time constant for cytosolic Ca2+ removal (tau(Ca)). tau Ca was prolonged by just 35% in myocytes from failing hearts after fixed voltage steps in physiological solutions (tau(Ca) control, 216+/-25 ms, n=17; tau(Ca) failing, 292+/-23 ms, n=22; P