The Effects of Brain Injury on Heart Rate Variability and the Innate Immune Response in Critically III Patients
The Effects of Brain Injury on Heart Rate Variability and the Innate Immune Response in Critically III Patients
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DOI：
10.1089/neu.2011.2035
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发表时间：
2012-03-01
影响因子：
4.2
通讯作者：
Hoedemaekers, Cornelia W.
中科院分区：
文献类型：
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作者：
Kox, Matthijs;Vrouwenvelder, Maarten Q.;Hoedemaekers, Cornelia W.
脑损伤及其相关的颅内压（ICP）升高可能导致迷走神经活动增加，随后通过胆碱能抗炎途径抑制先天性免疫。这可能解释了在这些患者中观察到的感染易感性增加。在本研究中，我们调查了脑损伤，迷走神经活动和先天免疫之间的关系。我们确定心率变异性（HRV）作为衡量迷走神经活动，血浆细胞因子和离体脂多糖刺激的全血中的细胞因子产生的34例患者在入院的前4天的神经重症监护病房（ICU）的各种形式的脑损伤。在整个患者组和高ICP（颅内出血[ ICH]）和正常ICP（蛛网膜下腔出血[ SAH]伴脑室外引流缓解ICP）相关疾病患者亚组中分析HRV、免疫参数以及这些指标之间的相关性。健康志愿者用于比较。与健康志愿者相比，患者的HRV总频谱功率和体外刺激的细胞因子产生严重降低（p < 0.05）。此外，HRV分析显示，与健康志愿者相比，患者的高频功率标准化单位（HFnu，对应于迷走神经活动）较高，低频：高频比率（LF：HF，对应于交感迷走神经平衡）较低（p < 0.05）。HFnu与体外刺激的肿瘤坏死因子-α（TNF-α）产生呈负相关（r =-0.22，p = 0.025）。在ICH组中观察到离体刺激的细胞因子产生的最明显抑制。此外，在ICH患者中，HFnu与较低的血浆TNF-α水平密切相关（r =-0.73，p = 0.002）。我们的数据表明，脑损伤，特别是与ICP增加相关的疾病，与迷走神经介导的免疫抑制有关。
Brain injury and its related increased intracranial pressure (ICP) may lead to increased vagus nerve activity and the subsequent suppression of innate immunity via the cholinergic anti-inflammatory pathway. This may explain the observed increased susceptibility to infection in these patients. In the present study, we investigated the association between brain injury, vagus nerve activity, and innate immunity. We determined heart rate variability (HRV) as a measure of vagus nerve activity, plasma cytokines, and cytokine production of ex vivo lipopolysaccharide-stimulated whole blood in the first 4 days of admission to the neurological intensive care unit (ICU) in 34 patients with various forms of brain damage. HRV, immune parameters, and the correlations between these measures were analyzed in the entire group of patients and in subgroups of patients with conditions associated with high (intracranial hemorrhage [ ICH]) and normal ICP (subarachnoid hemorrhage [ SAH] with an extraventricular drain alleviating ICP). Healthy volunteers were used for comparison. HRV total spectral power and ex vivo-stimulated cytokine production were severely depressed in patients compared with healthy volunteers (p < 0.05). Furthermore, HRV analysis showed that normalized units of high-frequency power (HFnu, corresponding with vagus nerve activity) was higher, and the low-frequency: high-frequency ratio (LF:HF, corresponding with sympathovagal balance) was lower in patients compared to healthy volunteers (p < 0.05). HFnu correlated inversely with ex vivo-stimulated tumor necrosis factor-alpha (TNF-alpha) production (r = -0.22, p = 0.025). The most pronounced suppression of ex vivo-stimulated cytokine production was observed in the ICH group. Furthermore, in ICH patients, HFnu correlated strongly with lower plasma TNF-alpha levels (r = -0.73, p = 0.002). Our data suggest that brain injury, and especially conditions associated with increased ICP, is associated with vagus nerve-mediated immune suppression.