Intracellular Ca2+ dynamics and the stability of ventricular tachycardia

被引:276
作者
Chudin, E
Goldhaber, J
Garfinkel, A
Weiss, J
Kogan, B
机构
[1] Univ Calif Los Angeles, Dept Comp Sci, Los Angeles, CA 90095 USA
[2] Univ Calif Los Angeles, Dept Biomath, Los Angeles, CA 90095 USA
[3] Univ Calif Los Angeles, Dept Med Cardiol, Los Angeles, CA 90095 USA
[4] Univ Calif Los Angeles, Dept Physiol, Los Angeles, CA 90095 USA
[5] Univ Calif Los Angeles, Dept Physiol Sci, Los Angeles, CA 90095 USA
关键词
D O I
10.1016/S0006-3495(99)77126-2
中图分类号
Q6 [生物物理学];
学科分类号
071011 ;
摘要
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.
引用
收藏
页码:2930 / 2941
页数:12
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