Munteanu Adelina, Kondratyev Aleksandar A, Kucera Jan P
Department of Physiology, University of Bern, Bern, Switzerland.
Biophys J. 2008 Feb 1;94(3):1094-109. doi: 10.1529/biophysj.107.113811. Epub 2007 Oct 5.
Reentry is a mechanism underlying numerous cardiac arrhythmias. During reentry, head-tail interactions of the action potential can cause cycle length (CL) oscillations and affect the stability of reentry. We developed a method based on a difference-delay equation to determine the slopes of the action potential duration and conduction velocity restitution functions, known to be major determinants of reentrant arrhythmogenesis, from the spatial period P and the decay length D of damped CL oscillations. Using this approach, we analyzed CL oscillations after the induction of reentry and the resetting of reentry with electrical stimuli in rings of cultured neonatal rat ventricular myocytes grown on microelectrode arrays and in corresponding simulations with the Luo-Rudy model. In the experiments, P was larger and D was smaller after resetting impulses compared to the induction of reentry, indicating that reentry became more stable. Both restitution slopes were smaller. Consistent with the experimental findings, resetting of simulated reentry caused oscillations with gradually increasing P, decreasing D, and decreasing restitution slopes. However, these parameters remained constant when ion concentrations were clamped, revealing that intracellular ion accumulation stabilizes reentry. Thus, the analysis of CL oscillations during reentry opens new perspectives to gain quantitative insight into action potential restitution.
折返是众多心律失常的潜在机制。在折返过程中,动作电位的首尾相互作用可导致周期长度(CL)振荡,并影响折返的稳定性。我们基于一个差分延迟方程开发了一种方法,根据阻尼CL振荡的空间周期P和衰减长度D来确定动作电位时程和传导速度恢复函数的斜率,已知这两个函数是折返性心律失常发生的主要决定因素。利用这种方法,我们分析了在微电极阵列上培养的新生大鼠心室肌细胞环中诱发折返后以及用电刺激重置折返时的CL振荡,并使用Luo-Rudy模型进行了相应的模拟。在实验中,与诱发折返相比,重置冲动后P更大而D更小,这表明折返变得更稳定。两个恢复斜率都更小。与实验结果一致,模拟折返的重置导致振荡,P逐渐增加,D减小,恢复斜率减小。然而,当离子浓度被钳制时,这些参数保持不变,这表明细胞内离子积累使折返稳定。因此,对折返期间CL振荡的分析为深入了解动作电位恢复提供了新的定量视角。