Sayk Friedhelm, Vietheer Alexander, Schaaf Bernhard, Wellhoener Peter, Weitz Gunther, Lehnert Hendrik, Dodt Christoph
Clinic for Internal Medicine I, Univ. Hospital of Schleswig-Holstein, Campus Luebeck, Ratzeburger Allee 160, 23538 Luebeck, Germany.
Am J Physiol Regul Integr Comp Physiol. 2008 Sep;295(3):R891-8. doi: 10.1152/ajpregu.90444.2008. Epub 2008 Jul 16.
Experimental endotoxemia as a model of the initial septic response affects the autonomic nervous system with profound cardiovascular sequelae. Whether the postsynaptic sympathoneural activity to the muscle vascular bed is altered in the early septic phase remains to be determined. The present study aimed to elucidate the early effects of LPS on muscle sympathetic nerve activity (MSNA) and cardiovascular regulation in healthy humans. Young, healthy volunteers randomly received either an LPS bolus (4 ng/kg body wt, n = 11) or placebo (saline; n = 7). Experimental baroreflex assessment (baseline measurements followed by infusion of vasoactive drugs nitroprusside/phenylephrine) was done prior to and 90 min following LPS or placebo challenge. MSNA, heart rate, blood pressure, and blood levels of catecholamines, TNF-alpha and IL-6 were measured sequentially. Endotoxin but not placebo-induced flu-like symptoms and elevated cytokine levels. In contrast to placebo, LPS significantly suppressed MSNA burst frequency 90 min after injection [mean +/- SE: 12.1 +/- 2.9 vs. 27.5 +/- 3.3 burst/min (post- vs. pre-LPS); P < 0.005] but increased heart rate [78.4 +/- 3.1 vs. 60.6 +/- 2.0 beats/min (post- vs. pre-LPS); P < 0.001]. Baseline blood pressure was not altered, but baroreflex testing demonstrated a blunted MSNA response and uncoupling of heart rate modulation to blood pressure changes in the endotoxin group. We conclude that endotoxin challenge in healthy humans has rapid suppressive effects on postsynaptic sympathetic nerve activity to the muscle vascular bed and alters baroreflex function which may contribute to the untoward cardiovascular effects of sepsis.
实验性内毒素血症作为初始脓毒症反应的模型，会影响自主神经系统，并引发严重的心血管后遗症。在脓毒症早期，肌肉血管床的突触后交感神经活动是否改变仍有待确定。本研究旨在阐明脂多糖（LPS）对健康人体肌肉交感神经活动（MSNA）和心血管调节的早期影响。年轻健康志愿者被随机分为两组，一组接受LPS推注（4 ng/kg体重，n = 11），另一组接受安慰剂（生理盐水；n = 7）。在LPS或安慰剂注射前及注射后90分钟进行实验性压力反射评估（先进行基线测量，然后输注血管活性药物硝普钠/去氧肾上腺素）。依次测量MSNA、心率、血压以及儿茶酚胺、肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）的血药浓度。内毒素而非安慰剂诱发了类似流感的症状并提高了细胞因子水平。与安慰剂相比，LPS在注射后90分钟显著抑制了MSNA爆发频率[平均值±标准误：12.1±2.9次/分钟 vs. 27.5±3.3次/分钟（LPS注射后 vs. LPS注射前）；P < 0.005]，但提高了心率[78.4±3.1次/分钟 vs. 60.6±2.0次/分钟（LPS注射后 vs. LPS注射前）；P < 0.001]。基线血压未改变，但压力反射测试显示内毒素组的MSNA反应减弱，心率调节与血压变化解耦。我们得出结论，健康人体内的内毒素激发对肌肉血管床的突触后交感神经活动具有快速抑制作用，并改变压力反射功能，这可能导致脓毒症产生不良心血管效应。
