Preventing ventricular fibrillation by flattening cardiac restitution
Preventing ventricular fibrillation by flattening cardiac restitution
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DOI：
10.1073/pnas.090492697
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发表时间：
2000-05-23
影响因子：
11.1
通讯作者：
Chen, PS
中科院分区：
文献类型：
--
作者：
Garfinkel, A;Kim, YH;Chen, PS
心室颤动是心源性猝死的主要原因。在颤动中，碎片化的电波不规则地蜿蜒穿过心肌，造成紊乱且无效的收缩。理论和计算机研究以及最近的实验证据表明，颤动是由心脏动作电位持续时间的恢复特性（即其对先前舒张间隔的依赖性）产生和维持的。恢复假说指出，陡峭倾斜的恢复曲线会产生不稳定的波传播，从而导致波破裂，这是颤动所必需的事件。在这里，我们提出了支持这一想法的实验证据。特别是，我们将药物溴替铵的作用确定为未来开发有效的基于恢复的抗纤颤药物的原型。我们表明，溴烯的行为符合恢复假设：通过使恢复曲线变平，它可以防止波破裂，从而防止颤动。它甚至可以改变现有的颤动。要么进入周期性状态（室性心动过速，更容易控制），要么进入静止的健康组织。
Ventricular fibrillation is the leading cause of sudden cardiac death. In fibrillation, fragmented electrical waves meander erratically through the heart muscle, creating disordered and ineffective contraction. Theoretical and computer studies, as well as recent experimental evidence, have suggested that fibrillation is created and sustained by the property of restitution of the cardiac action potential duration (that is, its dependence on the previous diastolic interval). The restitution hypothesis states that steeply sloped restitution curves create unstable wave propagation that results in wave break, the event that is necessary for fibrillation. Here we present experimental evidence supporting this idea. In particular, we identify the action of the drug bretylium as a prototype for the future development of effective restitution-based antifibrillatory agents. We show that bretylium acts in accord with the restitution hypothesis: by flattening restitution curves, it prevents wave break and thus prevents fibrillation. It even converts existing fibrillation. either to a periodic state (ventricular tachycardia, which is much more easily controlled) or to quiescent healthy tissue.