Derksen Richard, van Rijen Harold V M, Wilders Ronald, Tasseron Sara, Hauer Richard N W, Rutten Willem L C, de Bakker Jacques M T
Heart Lung Center Utrecht, University Medical Center, Utrecht, Netherlands.
Circulation. 2003 Aug 19;108(7):882-8. doi: 10.1161/01.CIR.0000081766.16185.28. Epub 2003 Jul 14.
The mechanism by which structural barriers promote wave break and fibrillation is unclear. Conduction velocity (CV) restitution is an important determinant of wave break. Abnormal CV restitution is associated with ventricular fibrillation in patients with heart disease and arises preferentially in fibrotic myocardium. We hypothesize that tissue discontinuities imposed by structural barriers cause abnormal CV restitution.
Tissue discontinuities were simulated in cultures of neonatal rat heart cells grown in 8-armed star patterns. Premature stimulation was applied at the extremity of 1 arm (n=12) while extracellular electrograms were recorded at 24 sites throughout the star. Action potentials were recorded at the following 3 sites: in the stimulated arm and at the discontinuity both proximal to and distal from the star center. Extracellular recordings revealed progressive increases in activation delay (indicative for abnormal CV restitution) only at the discontinuity from arms proximal to the star center. The mean increase in delay was 0.81+/-0.41 ms/10 ms for recording sites proximal to and 3.13+/-0.58 ms/10 ms for sites distal from this discontinuity. Depolarizing currents were determined in single cells during premature stimulation and for voltage configurations similar to those arising at the discontinuity. Both voltage-clamp measurements and computer simulations showed that delay at the discontinuity was associated with biphasic, prolonged activation and delayed inactivation of depolarizing current.
Tissue discontinuities cause abnormal CV restitution. Rapid increase in activation after an initial slow activation and delayed inactivation at the discontinuity lengthen the duration of depolarizing current and cause the abnormal restitution.
结构屏障促进波破碎和颤动的机制尚不清楚。传导速度（CV）恢复是波破碎的一个重要决定因素。异常的CV恢复与心脏病患者的心室颤动有关，且优先出现在纤维化心肌中。我们假设结构屏障造成的组织不连续性会导致异常的CV恢复。
在以八臂星形图案生长的新生大鼠心脏细胞培养物中模拟组织不连续性。在一条臂的末端施加过早刺激（n = 12），同时在整个星形图案的24个位点记录细胞外电图。在以下3个位点记录动作电位：在受刺激的臂中以及在星形中心近端和远端的不连续处。细胞外记录显示，仅在星形中心近端臂的不连续处激活延迟逐渐增加（表明CV恢复异常）。对于靠近该不连续处的记录位点，延迟的平均增加为0.81±0.41毫秒/10毫秒，而对于远离该不连续处的位点，延迟的平均增加为3.13±0.58毫秒/10毫秒。在过早刺激期间以及对于类似于在不连续处出现的电压配置，在单细胞中测定去极化电流。电压钳测量和计算机模拟均表明，不连续处的延迟与去极化电流的双相、延长激活和延迟失活有关。
组织不连续性导致异常的CV恢复。在初始缓慢激活后激活迅速增加以及在不连续处延迟失活会延长去极化电流的持续时间并导致异常恢复。
