Weiss J N, Garfinkel A, Karagueuzian H S, Qu Z, Chen P S
Department of Medicine, UCLA Cardiovascular Research Laboratory, UCLA School of Medicine and Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Circulation. 1999 Jun 1;99(21):2819-26. doi: 10.1161/01.cir.99.21.2819.
Sudden cardiac death resulting from ventricular fibrillation can be separated into 2 components: initiation of tachycardia and degeneration of tachycardia to fibrillation. Clinical drug studies such as CAST and SWORD demonstrated that focusing exclusively on the first component is inadequate as a therapeutic modality. The hope for developing effective pharmacological therapy rests on a comprehensive understanding of the second component, the transition from tachycardia to fibrillation. We summarize evidence that the transition from tachycardia to fibrillation is a transition to spatiotemporal chaos, with similarities to the quasiperiodic transition to chaos seen in fluid turbulence. In this scenario, chaos results from the interaction of multiple causally independent oscillatory motions. Simulations in 2-dimensional cardiac tissue suggest that the destabilizing oscillatory motions during spiral-wave reentry arise from restitution properties of action potential duration and conduction velocity. The process of spiral-wave breakup in simulated cardiac tissue predicts remarkably well the sequence by which tachycardia degenerates to fibrillation in real cardiac tissue. Modifying action potential duration and conduction velocity restitution characteristics can prevent spiral-wave breakup in simulated cardiac tissue, suggesting that drugs with similar effects in real cardiac tissue may have antifibrillatory efficacy (the Restitution Hypothesis). If valid for the real heart, the Restitution Hypothesis will support a new paradigm for antiarrhythmic drug classification, incorporating an antifibrillatory profile based on effects on cardiac restitution and the traditional antitachycardia profile (classes 1 through 4).
心动过速的起始和心动过速恶化为颤动。诸如CAST和SWORD等临床药物研究表明，仅关注第一部分作为一种治疗方式是不够的。开发有效药物治疗的希望在于全面理解第二部分，即从心动过速到颤动的转变。我们总结了证据，表明从心动过速到颤动的转变是向时空混沌的转变，类似于在流体湍流中看到的从准周期到混沌的转变。在这种情况下，混沌是由多个因果独立的振荡运动相互作用产生的。二维心脏组织中的模拟表明，螺旋波折返期间的不稳定振荡运动源于动作电位持续时间和传导速度的恢复特性。模拟心脏组织中螺旋波破裂的过程非常准确地预测了心动过速在真实心脏组织中恶化为颤动的顺序。改变动作电位持续时间和传导速度恢复特性可以防止模拟心脏组织中的螺旋波破裂，这表明在真实心脏组织中具有类似作用的药物可能具有抗颤动疗效（恢复假说）。如果恢复假说对真实心脏有效，它将支持一种新的抗心律失常药物分类范式，纳入基于对心脏恢复的影响的抗颤动特征以及传统的抗心动过速特征（1至4类）。
