Biomedical Engineering, Rutgers University, Piscataway.
Shock. 2011 Mar;35(3):229-39. doi: 10.1097/SHK.0b013e318200032b.
The systemic inflammatory response syndrome often accompanies critical illnesses and can be an important cause of morbidity and mortality. Marked abnormalities in cardiovascular function accompany acute illnesses manifested as sustained tachyarrhythmias, which are but one component of systemic dysregulation. The realization that cardiac pacemaker activity is under control of the autonomic nervous system has promoted the analysis of heart rate (HR) variation for assessing autonomic activities. In acute illnesses, autonomic imbalance manifesting in part as parasympathetic attenuation is associated with increased morbidity in patients who manifest systemic inflammatory response syndrome phenotype. Driven by the premise that biological phenotypes emerge as the outcome of the coordinated action of network elements across the host, a multiscale model of human endotoxemia, as a prototype model of systemic inflammation in humans, is developed that quantifies critical aspects of the complex relationship between inflammation and autonomic HR regulation. In the present study, changes in HR response to acute injury, phenotypically expressed as tachycardia, are simulated as a result of autonomic imbalance that reflects sympathetic activity excess and parasympathetic attenuation. The proposed model assesses both the anti-inflammatory and cardiovascular effects of antecedent stresses upon the systemic inflammatory manifestations of human endotoxemia as well as a series of nonlinear inflammatory relevant scenarios. Such a modeling approach provides a comprehensive conceptual framework linking inflammation and physiological complexity via a multiscale model that may advance the translational potential of systems modeling in clinical research.
全身炎症反应综合征常伴随危重病发生，是发病率和死亡率升高的重要原因。心血管功能明显异常伴随着急性疾病出现，表现为持续的心动过速，这只是全身失调的一个组成部分。认识到心脏起搏器的活动受自主神经系统的控制，促进了心率（HR）变化的分析，以评估自主活动。在急性疾病中，自主神经失衡表现为副交感神经衰减，与表现出全身炎症反应综合征表型的患者发病率增加有关。基于这样的前提，即生物表型是宿主中网络元素协调作用的结果，开发了人类内毒素血症的多尺度模型，作为人类全身炎症的原型模型，定量描述了炎症和自主 HR 调节之间复杂关系的关键方面。在本研究中，模拟了 HR 对急性损伤的反应变化，表现为心动过速，这是自主神经失衡的结果，反映了交感神经活动过度和副交感神经衰减。所提出的模型评估了先前应激对人类内毒素血症全身炎症表现的抗炎和心血管作用，以及一系列非线性炎症相关情况。这种建模方法提供了一个全面的概念框架，通过多尺度模型将炎症和生理复杂性联系起来，可能会提高系统建模在临床研究中的转化潜力。
