Physiological genomics
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Physiological genomics · Aug 2011
Modeling autonomic regulation of cardiac function and heart rate variability in human endotoxemia.
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. ⋯ 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.