Intracellular Ca2+ dynamics and the stability of ventricular tachycardia
Intracellular Ca2+ dynamics and the stability of ventricular tachycardia
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DOI：
10.1016/s0006-3495(99)77126-2
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发表时间：
1999-12-01
影响因子：
3.4
通讯作者：
Kogan, B
中科院分区：
文献类型：
--
作者：
Chudin, E;Goldhaber, J;Kogan, B
室性颤动（VF）是心源性猝死的主要原因，通常在室性心动过速（VT）之前发生，但从室性心动过速过渡到室性心动过速的机制尚不清楚。细胞内Ca2+超载发生在VT典型的快速心率期间，也已知可促进心律失常。因此，我们使用实验和数学建模相结合的方法研究了细胞内Ca2+动力学在从VT到VF转变中的作用。结果表明：1)35℃下兔心室肌细胞快速起搏导致细胞内Ca2+水平升高，动作电位（AP）配置和细胞内Ca2+瞬态的复杂模式；2) Ca2+瞬态的复杂模式直接源于细胞内Ca2+循环的动态，而不仅仅是对搏动AP变化的被动反应；3)改良后的细胞内Ca2+动态的Luo-Rudy （LR）心室动作电位模拟了复杂的Ca2+动态，与离体肌细胞的实验结果吻合较好；4)当加入到模拟的二维心脏组织中时，该动作电位模型产生了一种从VT到vf样状态的螺旋波破裂形式，其中细胞内Ca2+动力学通过其对Ca2+敏感的膜电流(如/(Ca), /(NaCa))的影响发挥了关键作用。和/ (ns (Ca))。从某种程度上说，螺旋波破裂可以作为从VT到VF转变的模型，这些发现表明细胞内Ca2+动力学可能在VT的不稳定和向VF退化中起重要作用。
Ventricular fibrillation (VF), the major cause of sudden cardiac death, is typically preceded by ventricular tachycardia (VT) but the mechanisms underlying the transition from VT to VF are poorly understood. Intracellular Ca2+ overload occurs during rapid heart rates typical of VT and is also known to promote arrhythmias. We therefore studied the role of intracellular Ca2+ dynamics in the transition from VT to VF, using a combined experimental and mathematical modeling approach. Our results show that I) rapid pacing of rabbit ventricular myocytes at 35 degrees C led to increased intracellular Ca2+ levels and complex patterns of action potential (AP) configuration and the intracellular Ca2+ transients; 2) the complex patterns of the Ca2+ transient arose directly from the dynamics of intracellular Ca2+ cycling, and were not merely passive responses to beat-to-beat alterations in AP; 3) the complex Ca2+ dynamics were simulated in a modified version of the Luo-Rudy (LR) ventricular action potential with improved intracellular Ca2+ dynamics, and showed good agreement with the experimental findings in isolated myocytes; and 4) when incorporated into simulated two-dimensional cardiac tissue, this action potential model produced a form of spiral wave breakup from VT to a VF-like state in which intracellular Ca2+ dynamics played a key role through its influence on Ca2+-sensitive membrane currents such as /(Ca), /(NaCa),. and /(ns(Ca)). To the extent that spiral wave breakup is useful as a model for the transition from VT to VF, these findings suggest that intracellular Ca2+ dynamics may play an important role in the destabilization of VT and its degeneration into VF.