Pathogen-induced heart rate changes associated with cholinergic nervous system activation
Pathogen-induced heart rate changes associated with cholinergic nervous system activation
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DOI：
10.1152/ajpregu.00487.2010
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发表时间：
2011-02-01
影响因子：
2.8
通讯作者：
Goehler, Lisa E.
中科院分区：
文献类型：
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作者：
Fairchild, Karen D.;Srinivasan, Varadamurthy;Goehler, Lisa E.
费尔柴尔德KD，斯里尼瓦桑V，穆尔曼JR，盖伊克马RP，戈勒勒LE。与胆碱能神经系统激活相关的病原体诱导的心率变化。《美国生理学杂志：调节、整合与比较生理学》300卷：R330 - R339，2011年。首次发表于2010年11月10日；doi:10.1152/ajpregu.00487.2010。——自主神经系统在宿主防御的调节以及对脓毒症的生理反应中起着核心作用，包括心率和心率变异性的变化。胆碱能抗炎反应是指感染触发迷走神经传出信号，抑制促炎细胞因子的产生，预计这会导致向心脏的迷走神经信号增加以及心率变异性增加。事实上，心率变异性降低在脓毒症患者中被广泛描述。我们的研究通过表明注射病原体的小鼠在心率变异性（HRV）降低的背景下表现出迷走神经源性的短暂性心律失常，从而阐明了这一明显的矛盾。腹腔内注射大量革兰氏阳性或革兰氏阴性细菌或白色念珠菌会迅速诱发窦性和房室结阻滞的心律失常，这是心脏迷走神经放电的特征，并显著增加短期HRV。这些病原体诱导的心动过缓可被阿托品（一种毒蕈碱胆碱能受体拮抗剂）立即终止，这表明了迷走神经传出信号在这种反应中的作用。病原体注射后迷走神经传入信号通过迷走神经感觉神经节和脑干神经元中强烈的核c - Fos活性得以证明。令人惊讶的是，病原体诱导的心动过缓表现出快速且持久的脱敏现象，并且在初次接触后3小时或3天再次注射相同病原体时不会复发。在从初次心动过缓恢复后，一些小鼠出现心率变异性降低，并与血浆细胞因子水平升高和死亡率相关。我们在感染小鼠中发现的HRV降低和短暂的心率减速与我们小组在脓毒症早产儿中描述的心率变化相似。通过迷走神经的病原体感知和信号传导以及这种反应的脱敏现象，可能解释了脓毒症中心率变异性增加和降低的时期。
Fairchild KD, Srinivasan V, Moorman JR, Gaykema RP, Goehler LE. Pathogen-induced heart rate changes associated with cholinergic nervous system activation. Am J Physiol Regul Integr Comp Physiol 300: R330-R339, 2011. First published November 10, 2010; doi: 10.1152/ajpregu.00487.2010.-The autonomic nervous system plays a central role in regulation of host defense and in physiological responses to sepsis, including changes in heart rate and heart rate variability. The cholinergic anti-inflammatory response, whereby infection triggers vagal efferent signals that dampen production of proinflammatory cytokines, would be predicted to result in increased vagal signaling to the heart and increased heart rate variability. In fact, decreased heart rate variability is widely described in humans with sepsis. Our studies elucidate this apparent paradox by showing that mice injected with pathogens demonstrate transient bradyarrhythmias of vagal origin in a background of decreased heart rate variability (HRV). Intraperitoneal injection of a large inoculum of Gram-positive or Gram-negative bacteria or Candida albicans rapidly induced bradyarrhythmias of sinus and AV nodal block, characteristic of cardiac vagal firing and dramatically increased short-term HRV. These pathogen-induced bradycardias were immediately terminated by atropine, an antagonist of muscarinic cholinergic receptors, demonstrating the role of vagal efferent signaling in this response. Vagal afferent signaling following pathogen injection was demonstrated by intense nuclear c-Fos activity in neurons of the vagal sensory ganglia and brain stem. Surprisingly, pathogen-induced bradycardia demonstrated rapid and prolonged desensitization and did not recur on repeat injection of the same organism 3 h or 3 days after the initial exposure. After recovery from the initial bradycardia, depressed heart rate variability developed in some mice and was correlated with elevated plasma cytokine levels and mortality. Our findings of decreased HRV and transient heart rate decelerations in infected mice are similar to heart rate changes described by our group in preterm neonates with sepsis. Pathogen sensing and signaling via the vagus nerve, and the desensitization of this response, may account for periods of both increased and decreased heart rate variability in sepsis.