Excito-oscillatory dynamics as a mechanism of ventricular fibrillation
Excito-oscillatory dynamics as a mechanism of ventricular fibrillation
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DOI：
10.1016/j.hrthm.2008.01.011
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发表时间：
2008-04-01
期刊：
影响因子：
5.5
通讯作者：
Huelsing, Deilah J.
中科院分区：
文献类型：
--
作者：
Gray, Richard A.;Huelsing, Deilah J.
背景技术与折返螺旋波相关的不稳定性对于快速心律失常、特别是心室颤动(Vf)的引发和维持至关重要。除了组织异质性之外，螺旋波破碎只有一些基本的机制，最显着的是恢复。目的我们测试振荡膜特性会破坏螺旋波稳定性的假设。方法我们使用恒流刺激方案记录离体兔肌细胞的跨膜电位 (V,)。我们开发了一个数学模型，其中包括静息 V-m (-80 mV) 时的稳定兴奋平衡点和升高 V-m (-10 mV) 时的不稳定振荡平衡点。使用该模型的变体在二维网格中研究了螺旋波动力学。结果所有模型都显示出恢复状态并再现了静息和动作电位平台期间跨膜阻力的实验值。当模型仅显示 1 个平衡点时，观察到稳定的螺旋波。然而，如果模型同时显示可兴奋和振荡平衡点（即兴奋振荡模型），则观察到时空复杂性。最初的波破裂是由于振荡波向各个方向扩展所致；几次心跳后，这些模式的特征是不稳定的螺旋波和目标模式的组合，与 VF 期间在心脏表面观察到的模式一致。在我们的模型中，这种类 VF 活动仅在 V 振荡的单细胞周期在特定范围内时发生。 结论 在我们的兴奋振荡模型中观察到的类 VF 模式无法用现有提出的不稳定机制来解释。我们的结果提出了一个重要的建议，即负责 V 的膜动力学，在升高的 V 水平下振荡可以破坏螺旋波的稳定，因此可能是预防 VF 的新治疗靶点。
BACKGROUND The instabilities associated with reentrant spiral waves are of paramount importance to the initiation and maintenance of tachyarrhythmias, especially ventricular fibrillation (Vf). In addition to tissue heterogeneities, there are only a few basic purported mechanisms of spiral wave breakup, most notably restitution.OBJECTIVE We test the hypothesis that oscillatory membrane properties act to destabilize spiral waves.METHODS We recorded transmembrane potential (V,) from isolated rabbit myocytes using a constant current stimulation protocol. We developed a mathematical model that included both the stable excitable equilibrium point at resting V-m (-80 mV) and the unstable oscillatory equilibrium point at elevated V-m (-10 mV). Spiral wave dynamics were studied in 2-dimensional grids using variants of the model.RESULTS All models showed restitution and reproduced the experimental values of transmembrane resistance at rest and during the action potential plateau. Stable spiral waves were observed when the model showed only 1 equilibrium point. However, spatio-temporal complexity was observed if the model showed both excitable and oscillatory equilibrium points (i.e., excito-oscillatory models). The initial wave breaks resulted from oscillatory waves expanding in all directions; after a few beats, the patterns were characterized by a combination of unstable spiral waves and target patterns consistent with the patterns observed on the heart surface during VF. In our model, this VF-tike activity only occurred when the single cell period of V, oscillations was within a specific range.CONCLUSION The VF-Like patterns observed in our excito-oscillatory models could not be explained by the existing proposed instability mechanisms. Our results introduce the important suggestion that membrane dynamics responsible for V, oscillations at elevated V, levels can destabilize spiral waves and thus may be a novel therapeutic target for preventing VF.