The dynamic interaction of systemic inflammation and the hypothalamic-pituitary-adrenal (HPA) axis during and after major surgery
The dynamic interaction of systemic inflammation and the hypothalamic-pituitary-adrenal (HPA) axis during and after major surgery
复制标题
大手术期间和之后全身炎症与下丘脑-垂体-肾上腺（HPA）轴的动态相互作用
DOI：
10.1101/2021.08.16.456512
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Galvis D
中科院分区：
文献类型：
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作者：
Galvis D
大手术和危重疾病会产生可能危及生命的全身炎症反应。下丘脑-垂体-肾上腺（HPA）轴是通过促肾上腺皮质激素（ACTH）和皮质醇的变化来平衡这种全身炎症的关键生理系统之一。这些激素通常表现出高度相关的超昼夜脉动幅度调制的昼夜过程。然而，这些动态被大手术和危重疾病破坏。在这项工作中，我们的特点是炎症，ACTH和皮质醇反应的患者接受心脏手术，并表明HPA轴的反应可以分为三种表型之一：单脉冲，双脉冲和多脉冲动力学。我们开发了一个皮质醇分泌和代谢的数学模型，预测负责这些不同的表型的生理机制。我们发现，炎症介质的影响是重要的，只有在单脉冲模式，其中正常的脉动是丢失，这表明这种表型可能是最大的炎症反应的指示。调查这些表型是否以及如何与临床结果相关，对患者预后和设计改善恢复的干预措施至关重要。
Major surgery and critical illness produce a potentially life-threatening systemic inflammatory response. The hypothalamic–pituitary–adrenal (HPA) axis is one of the key physiological systems that counterbalances this systemic inflammation through changes in adrenocorticotrophic hormone (ACTH) and cortisol. These hormones normally exhibit highly correlated ultradian pulsatility with an amplitude modulated by circadian processes. However, these dynamics are disrupted by major surgery and critical illness. In this work, we characterize the inflammatory, ACTH and cortisol responses of patients undergoing cardiac surgery and show that the HPA axis response can be classified into one of three phenotypes: single-pulse, two-pulse and multiple-pulse dynamics. We develop a mathematical model of cortisol secretion and metabolism that predicts the physiological mechanisms responsible for these different phenotypes. We show that the effects of inflammatory mediators are important only in the single-pulse pattern in which normal pulsatility is lost—suggesting that this phenotype could be indicative of the greatest inflammatory response. Investigating whether and how these phenotypes are correlated with clinical outcomes will be critical to patient prognosis and designing interventions to improve recovery.