Phadumdeo Vrishti M, Weinberg Seth H
Department of Biomedical Engineering, Virginia Commonwealth University, 601 W. Main Street, Richmond, VA 23284, United States.
Department of Biomedical Engineering, Virginia Commonwealth University, 601 W. Main Street, Richmond, VA 23284, United States. Electronic address: http://www.shweinberglab.com.
J Theor Biol. 2018 Apr 7;442:31-43. doi: 10.1016/j.jtbi.2018.01.007. Epub 2018 Jan 11.
Heart rate continuously varies due to autonomic regulation, stochasticity in pacemaking, and circadian rhythm, collectively termed heart rate variability (HRV), during normal physiological conditions. Low HRV is clinically associated with an elevated risk of cardiac arrhythmias. Alternans, a beat-to-beat alternation in action potential duration (APD) and/or intracellular calcium (Ca) transient, is a well-known risk factor associated with cardiac arrhythmias that is typically studied under conditions of a constant pacing rate, i.e., the absence of HRV. In this study, we investigate the effects of HRV on the interplay between APD, Ca, and electromechanical properties, employing a nonlinear discrete-time map model that governs APD and intracellular Ca cycling with a stochastic pacing period. We find that HRV can decrease variation in APD and peak Ca at fast pacing rates for which alternans is present. Further, increased HRV typically disrupts the alternating pattern for both APD and peak Ca and weakens the correlation between APD and peak Ca, thus decoupling Ca-mediated instabilities from repolarization alternation. We find that the efficacy of these effects is regulated by the sarcoplasmic reticulum Ca uptake rate. Overall, these results demonstrate that HRV disrupts arrhythmogenic alternans and suggests that HRV may be a significant factor in preventing life-threatening arrhythmias.
在正常生理条件下，由于自主神经调节、起搏的随机性和昼夜节律，心率持续变化，这些因素统称为心率变异性（HRV）。低HRV在临床上与心律失常风险升高相关。复极交替现象，即动作电位时程（APD）和/或细胞内钙（Ca）瞬变的逐搏交替，是一种与心律失常相关的众所周知的危险因素，通常在恒定起搏频率条件下（即不存在HRV的情况下）进行研究。在本研究中，我们使用一个非线性离散时间映射模型来研究HRV对APD、Ca和机电特性之间相互作用的影响，该模型通过随机起搏周期来控制APD和细胞内钙循环。我们发现，对于存在复极交替现象的快速起搏频率，HRV可以降低APD和钙峰值的变化。此外，HRV增加通常会破坏APD和钙峰值的交替模式，并削弱APD与钙峰值之间的相关性，从而使钙介导的不稳定性与复极化交替解耦。我们发现这些效应的效力受肌浆网钙摄取率的调节。总体而言，这些结果表明HRV会破坏致心律失常的复极交替现象，并提示HRV可能是预防危及生命的心律失常的一个重要因素。
