Chaos and the transition to ventricular fibrillation - A new approach to antiarrhythmic drug evaluation
Chaos and the transition to ventricular fibrillation - A new approach to antiarrhythmic drug evaluation
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DOI：
10.1161/01.cir.99.21.2819
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发表时间：
1999-06-01
期刊：
影响因子：
37.8
通讯作者：
Chen, PS
中科院分区：
文献类型：
--
作者：
Weiss, JN;Garfinkel, A;Chen, PS
室颤引起的心源性猝死可分为2个部分：心动过速的开始和心动过速退化为室颤。CAST和SWORD等临床药物研究表明，仅关注第一种成分作为治疗方式是不够的。开发有效的药物治疗的希望在于对第二个组成部分的全面理解，即从心动过速到纤颤的转变。我们总结的证据表明，从心动过速到纤颤的过渡是一个过渡到时空混沌，与流体湍流中看到的准周期性过渡到混沌的相似之处。在这种情况下，混沌的结果从多个因果独立的振荡运动的相互作用。二维心脏组织的模拟表明，不稳定的振荡运动在螺旋波折返引起的动作电位时程和传导速度的恢复特性。模拟心脏组织中螺旋波分裂的过程可以很好地预测心动过速在真实的心脏组织中退化为纤颤的顺序。修改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，这表明在真实的心脏组织中具有类似作用的药物可能具有抗心律失常的功效（恢复假说）。如果对真实的心脏有效，恢复假说将支持抗心动过速药物分类的新范式，将基于对心脏恢复的影响的抗心动过速特征和传统的抗心动过速特征（1至4类）结合起来。
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).