Modeling autonomic regulation of cardiac function and heart rate variability in human endotoxemia.
Modeling autonomic regulation of cardiac function and heart rate variability in human endotoxemia.
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DOI：
10.1152/physiolgenomics.00040.2011
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发表时间：
2011-08
影响因子：
4.6
通讯作者：
J. D. Scheff;P. D. Mavroudis;S. Calvano;S. Lowry;I. Androulakis
中科院分区：
文献类型：
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作者：
J. D. Scheff;P. D. Mavroudis;S. Calvano;S. Lowry;I. Androulakis
心率变异性（HRV）是心跳间变异性的量化指标，已被研究作为炎症性疾病（如败血症）的潜在预后指标。心率变异性通常反映了体内平衡的显著变化水平，这种变化在压力下可能会消失。从定量理解应激源如何改变HRV动力学的角度来解释HRV已经做了很多努力，但是引起稳态HRV和HRV变化的分子和细胞机制却很少受到关注。在这里，我们开发了一个数学模型的人类内毒素血症，包括振荡信号引起的HRV和他们的信号传导到心脏。细胞、分子和神经水平上的过程之间的联系与HRV定量相关。代表自主振荡和昼夜节律的节律信号会聚以调节心跳模式，并且这些振荡器的作用在急性内毒素血症反应中减弱。基于本文开发的半机械模型，根据这些振荡信号研究了HRV的稳态和急性应激反应。了解内毒素血症中HRV的丢失是了解通过基于生物过程和临床结局之间关系的系统生物学转化应用临床观察到的HRV变化的一步。
Heart rate variability (HRV), the quantification of beat-to-beat variability, has been studied as a potential prognostic marker in inflammatory diseases such as sepsis. HRV normally reflects significant levels of variability in homeostasis, which can be lost under stress. Much effort has been placed in interpreting HRV from the perspective of quantitatively understanding how stressors alter HRV dynamics, but the molecular and cellular mechanisms that give rise to both homeostatic HRV and changes in HRV have received less focus. Here, we develop a mathematical model of human endotoxemia that incorporates the oscillatory signals giving rise to HRV and their signal transduction to the heart. Connections between processes at the cellular, molecular, and neural levels are quantitatively linked to HRV. Rhythmic signals representing autonomic oscillations and circadian rhythms converge to modulate the pattern of heartbeats, and the effects of these oscillators are diminished in the acute endotoxemia response. Based on the semimechanistic model developed herein, homeostatic and acute stress responses of HRV are studied in terms of these oscillatory signals. Understanding the loss of HRV in endotoxemia serves as a step toward understanding changes in HRV observed clinically through translational applications of systems biology based on the relationship between biological processes and clinical outcomes.