Wang Yanggan, Cheng Jun, Joyner Ronald W, Wagner Mary B, Hill Joseph A
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Circulation. 2006 Apr 18;113(15):1849-56. doi: 10.1161/CIRCULATIONAHA.106.615682.
The early phase of action potential (AP) repolarization is critical to impulse conduction in the heart because it provides current for charging electrically coupled cells. In the present study we tested the impact of heart failure-associated electrical remodeling on AP propagation.
Subepicardial, midmyocardial, and subendocardial myocytes were enzymatically dissociated from control and pressure-overload failing left ventricle (LV), and APs were recorded. A unique coupling-clamp technique was used to electrically couple 2 isolated myocytes with a controlled value of coupling conductance (Gc). In sham-operated mice, AP duration manifested a clear transmural gradient, with faster repolarization in subepicardial myocytes than in subendocardial myocytes. AP propagation from subendocardial to subepicardial myocytes required less Gc compared with conduction in the opposite direction. In failing heart, AP morphology was dramatically altered, with a significantly elevated plateau potential and prolonged AP duration. Spatially nonuniform alteration of AP duration in failing heart blunted the transmural gradient of repolarization. Furthermore, increased pacing rate prolonged AP duration exclusively in myocytes from failing heart, and the critical conductance required for successful AP propagation decreased significantly at high frequencies. Finally, in failing heart, asymmetry of transmural electrical propagation was abolished.
In failing heart, preferential conduction from subendocardial to subepicardial myocytes is lost, and failing myocytes manifest facilitated AP propagation at fast rates. Together, these electrical remodeling responses may promote conduction of premature impulses and heighten the risk of malignant arrhythmia, a prominent feature of heart failure.
动作电位（AP）复极化的早期阶段对心脏冲动传导至关重要，因为它为电耦合细胞充电提供电流。在本研究中，我们测试了心力衰竭相关的电重构对AP传播的影响。
从对照和压力超负荷衰竭的左心室（LV）中酶解分离出心外膜、心肌中层和心内膜下心肌细胞，并记录AP。使用一种独特的耦合钳技术将2个分离的心肌细胞以可控的耦合电导（Gc）值进行电耦合。在假手术小鼠中，AP持续时间表现出明显的跨壁梯度，心外膜下心肌细胞的复极化比心内膜下心肌细胞更快。与相反方向的传导相比，从心内膜下心肌细胞到心外膜下心肌细胞的AP传播所需的Gc较小。在衰竭心脏中，AP形态发生显著改变，平台电位显著升高，AP持续时间延长。衰竭心脏中AP持续时间的空间不均匀改变使复极化的跨壁梯度变钝。此外，增加起搏频率仅使衰竭心脏的心肌细胞的AP持续时间延长，并且在高频时成功AP传播所需的临界电导显著降低。最后，在衰竭心脏中，跨壁电传播的不对称性消失。
在衰竭心脏中，心内膜下心肌细胞到心外膜下心肌细胞的优先传导丧失，衰竭的心肌细胞在快速率下表现出促进的AP传播。总之，这些电重构反应可能促进过早冲动的传导并增加恶性心律失常的风险，这是心力衰竭的一个突出特征。
