Department of Physiology, University of Bern, Bern, Switzerland.
Biophys J. 2010 Apr 7;98(7):1129-38. doi: 10.1016/j.bpj.2009.12.4280.
Cardiac restitution is an important factor in arrhythmogenesis. Steep positive action potential duration and conduction velocity (CV) restitution slopes promote alternans and reentrant arrhythmias. We examined the consequences of supernormal conduction (characterized by a negative CV restitution slope) on patterns of conduction and alternans in strands of Luo-Rudy model cells and in cultured cardiac cell strands. Interbeat intervals (IBIs) were analyzed as a function of distance during S1S2 protocols and during pacing at alternating cycle lengths. Supernormal conduction was induced by decreasing K(+). In control K(+) simulations, S1S2 intervals converged toward basic cycle length with a length constant determined by both CV and the CV restitution slope. During alternant pacing, the amplitude of IBI alternans converged with a shorter length constant, determined also by the action potential duration restitution slope. In contrast, during supernormal conduction, S1S2 intervals and the amplitude of alternans diverged. This amplification (resonance) led to phase-locked or more complex alternans patterns, and then to distal conduction block. The convergence/divergence of IBIs was verified in the cultured strands, in which naturally occurring tissue heterogeneities resulted in prominent discontinuities of the spatial IBI profiles. We conclude that supernormal conduction potentiates alternans and spatial analysis of IBIs represents a powerful method to locate tissue heterogeneities.
心脏复极是心律失常发生的一个重要因素。正性动作电位时程和传导速度(CV)复极斜率陡峭会促进折返性心律失常和交替性心律失常。我们研究了超常传导(表现为 CV 复极斜率为负)对洛鲁迪模型细胞和培养的心肌细胞束中传导和交替性的影响。在 S1S2 方案和交替周长起搏期间,通过分析心搏间期(IBI)与距离的关系来研究。通过降低 K(+)来诱导超常传导。在对照 K(+)模拟中,S1S2 间隔以基本周期长度为收敛,长度常数由 CV 和 CV 复极斜率共同决定。在交替起搏时,IBI 交替的幅度以更短的长度常数收敛,该常数也由动作电位时程复极斜率决定。相比之下,在超常传导时,S1S2 间隔和交替的幅度发散。这种放大(共振)导致锁相或更复杂的交替模式,然后导致远端传导阻滞。IBI 的收敛/发散在培养的细胞束中得到了验证,其中自然发生的组织异质性导致空间 IBI 曲线的明显不连续。我们得出结论,超常传导增强了交替性,IBI 的空间分析是定位组织异质性的一种有力方法。