Endotoxin depresses heart rate variability in mice: cytokine and steroid effects
Endotoxin depresses heart rate variability in mice: cytokine and steroid effects
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DOI：
10.1152/ajpregu.00132.2009
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发表时间：
2009-10-01
影响因子：
2.8
通讯作者：
Moorman, J. Randall
中科院分区：
文献类型：
--
作者：
Fairchild, Karen D.;Saucerman, Jeffrey J.;Moorman, J. Randall
费尔柴尔德KD，索克曼JJ，雷诺LL，西瓦克JA，肖Y，莱克DE，莫尔曼JR。内毒素降低小鼠心率变异性：细胞因子和类固醇的作用。《美国生理学杂志 - 调节、整合与比较生理学》297卷：R1019 - R1027，2009年。首次发表于2009年8月5日；doi:10.1152/ajpregu.00132.2009。 - 心率变异性（HRV）在脓毒症患者中下降，但其机制尚未完全明确。我们利用内毒素血症小鼠模型来验证细胞因子在脓毒症期间异常HRV中起作用这一假设。成年雄性C57BL/6小鼠通过手术植入探头，利用无线电遥测技术持续监测心电图、体温或血压。给予高剂量脂多糖（大肠杆菌脂多糖，10 mg/kg，n = 10）引起双相反应，表现为部分小鼠在1小时时体温和心率早期下降，随后所有小鼠的HRV长时间降低。进一步研究表明，低至0.01 mg/kg的脂多糖剂量也会引起HRV显著下降。对于高剂量脂多糖，体温和心率的初始下降与脂多糖注射后1小时肿瘤坏死因子α的峰值表达在时间上相关，而HRV的最大降幅与脂多糖注射后3 - 9小时多种其他细胞因子的峰值水平一致。低血压和低体温都不能解释HRV反应。在脂多糖注射前用地塞米松预处理显著减弱了所研究的10种细胞因子中7种的表达，并使HRV降低的持续时间缩短约一半。有趣的是，单独使用地塞米松治疗导致低频和高频HRV大幅增加。给予重组肿瘤坏死因子α引起心率和HRV的双相反应，与脂多糖引起的反应相似。了解细胞因子在脓毒症期间异常HRV中的作用可能会为检测重症监护病房患者危及生命的医院感染带来改进的策略。
Fairchild KD, Saucerman JJ, Raynor LL, Sivak JA, Xiao Y, Lake DE, Moorman JR. Endotoxin depresses heart rate variability in mice: cytokine and steroid effects. Am J Physiol Regul Integr Comp Physiol 297: R1019-R1027, 2009. First published August 5, 2009; doi: 10.1152/ajpregu.00132.2009.-Heart rate variability (HRV) falls in humans with sepsis, but the mechanism is not well understood. We utilized a mouse model of endotoxemia to test the hypothesis that cytokines play a role in abnormal HRV during sepsis. Adult male C57BL/6 mice underwent surgical implantation of probes to continuously monitor electrocardiogram and temperature or blood pressure via radiotelemetry. Administration of high-dose LPS (Escherichia coli LPS, 10 mg/kg, n = 10) caused a biphasic response characterized by an early decrease in temperature and heart rate at 1 h in some mice, followed by a prolonged period of depressed HRV in all mice. Further studies showed that LPS doses as low as 0.01 mg/kg evoked a significant decrease in HRV. With high-dose LPS, the initial drops in temperature and HR were temporally correlated with peak expression of TNF alpha 1 h post-LPS, whereas maximal depression in HRV coincided with peak levels of multiple other cytokines 3-9 h post-LPS. Neither hypotension nor hypothermia explained the HRV response. Pretreatment with dexamethasone prior to LPS significantly blunted expression of 7 of the 10 cytokines studied and shortened the duration of depressed HRV by about half. Interestingly, dexamethasone treatment alone caused a dramatic increase in both low-and high-frequency HRV. Administration of recombinant TNF alpha caused a biphasic response in HR and HRV similar to that caused by LPS. Understanding the role of cytokines in abnormal HRV during sepsis could lead to improved strategies for detecting life-threatening nosocomial infections in intensive care unit patients.