ten Tusscher K H W J, Mourad A, Nash M P, Clayton R H, Bradley C P, Paterson D J, Hren R, Hayward M, Panfilov A V, Taggart P
Department of Scientific Computing, Simula Research Laboratory, Lysaker, Norway.
Exp Physiol. 2009 May;94(5):553-62. doi: 10.1113/expphysiol.2008.044065. Epub 2009 Jan 23.
Sudden cardiac death is a major health problem in the industrialized world. The lethal event is typically ventricular fibrillation (VF), during which the co-ordinated regular contraction of the heart is overthrown by a state of mechanical and electrical anarchy. Understanding the excitation patterns that sustain VF is important in order to identify potential therapeutic targets. In this paper, we studied the organization of human VF by combining clinical recordings of electrical excitation patterns on the epicardial surface during in vivo human VF with simulations of VF in an anatomically and electrophysiologically detailed computational model of the human ventricles. We find both in the computational studies and in the clinical recordings that epicardial surface excitation patterns during VF contain around six rotors. Based on results from the simulated three-dimensional excitation patterns during VF, which show that the total number of electrical sources is 1.4 +/- 0.12 times greater than the number of epicardial rotors, we estimate that the total number of sources present during clinically recorded VF is 9.0 +/- 2.6. This number is approximately fivefold fewer compared with that observed during VF in dog and pig hearts, which are of comparable size to human hearts. We explain this difference by considering differences in action potential duration dynamics across these species. The simpler spatial organization of human VF has important implications for treatment and prevention of this dangerous arrhythmia. Moreover, our findings underline the need for integrated research, in which human-based clinical and computational studies complement animal research.
心脏性猝死是工业化国家的一个主要健康问题。致死事件通常为心室颤动（VF），在此期间，心脏协调一致的规则收缩被机械和电的无序状态所取代。了解维持心室颤动的兴奋模式对于确定潜在的治疗靶点很重要。在本文中，我们通过将人体心室颤动期间心外膜表面电兴奋模式的临床记录与人体心室详细解剖和电生理计算模型中的心室颤动模拟相结合，研究了人体心室颤动的组织情况。我们在计算研究和临床记录中均发现，心室颤动期间心外膜表面兴奋模式包含约六个转子。基于心室颤动期间模拟的三维兴奋模式结果，其显示电源总数比心外膜转子数多1.4±0.12倍，我们估计临床记录的心室颤动期间存在的电源总数为9.0±2.6。与在大小与人心脏相当的犬和猪心脏的心室颤动期间观察到的数量相比，这个数字大约少五倍。我们通过考虑这些物种之间动作电位持续时间动态的差异来解释这种差异。人体心室颤动更简单的空间组织对这种危险心律失常的治疗和预防具有重要意义。此外，我们的研究结果强调了综合研究的必要性，即基于人体的临床和计算研究应补充动物研究。
