In vivo interaction of endotoxin and recombinant bactericidal/permeability-increasing protein (rBPl23):: Hemodynamic effects in a human endotoxemia model
In vivo interaction of endotoxin and recombinant bactericidal/permeability-increasing protein (rBPl23):: Hemodynamic effects in a human endotoxemia model
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DOI：
10.1067/mlc.2002.127170
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发表时间：
2002-10-01
期刊：
影响因子：
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通讯作者：
Van Lieshout, JJ
中科院分区：
文献类型：
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作者：
Jellema, WT;Veerman, DP;Van Lieshout, JJ
在健康受试者中，内毒素引起的心血管紊乱在质量上与在感染性休克患者中观察到的相似。对内毒素的生物反应部分归因于细胞因子的释放。在实验性内毒素血症中，重组杀菌/通透性增加蛋白（rBPI(23)）通过与内毒素结合，抑制内毒素诱导的细胞因子释放和中性粒细胞活化，显示出保护作用。在一项对照、盲法交叉研究中，在实验性人类内毒素血症模型中研究了rBPI的早期心血管作用（23）。研究了8名健康成年男性在注射内毒素（40 EU/kg体重）和rBPI(23 EU/kg) （1 mg/kg）或安慰剂（人血清白蛋白，0.2 mg/kg） 2小时后动脉压和心输出量的搏动变化。单独使用内毒素或rBPI（23）不会引起明显的心血管变化。rBPI（23）输注内毒素后，大鼠外周血总阻力在4分钟后降至最低点，为对照水平的40%（范围16 ~ 53，P < 0.001）。平均动脉压变化不大，外周总阻力的下降与心率和心输出量的反射性增加有关（32%；范围43-106）。随后2小时的心血管变量变化不显著。分别评估了rBPI（23）、LPS和LPS-rBPI（23）复合物对接触系统的体外激活作用。与rBPI（23）、LPS和LPS-rBPI（23）复合物孵育后，复合物水平与缓冲对照中观察到的水平相当。内毒素与rBPI同时给予的快速血管扩张（23）不是由补体或接触系统激活介导的。早期血管舒张由心输出量增加所补偿，因此不会导致动脉低血压。持续心输出量的监测可以检测到在动脉压记录中未被注意到的对全身血流和传导的快速影响。
The cardiovascular derangement that results from the administration of endotoxin in healthy subjects is qualitatively similar to what is observed in patients in septic shock. The biological response to endotoxin is attributed in part to cytokine release. In experimental endotoxemia, recombinant bactericidal/permeability increasing protein (rBPI(23)) has shown a protective effect by binding endotoxin with the subsequent inhibition of the endotoxin-induced cytokine release and of neutrophil activation. In a controlled, blinded crossover study the early cardiovascular effects of rBPI(23) were investigated in an experimental endotoxemia model in humans. The beat-to-beat changes in arterial pressure and cardiac output following infusion of endotoxin (40 EU/kg body weight) and rBPI(23) (1 mg/kg) or placebo (human serum albumin, 0.2 mg/kg) were studied for 2 hours in 8 healthy male adults. Endotoxin or rBPI(23) alone did not induce significant cardiovascular changes. Endotoxin following rBPI(23) infusion elicited a fall in total peripheral resistance with its nadir after 4 minutes to 40% (range 16-53; P < .001) of control level. Mean arterial pressure showed little change, and the fall in total peripheral resistance was associated with a reflex increase in heart rate and cardiac output (32%; range 43-106). Changes in cardiovascular variables in the subsequent 2 hours were not significant. In vitro activation of the contact system by, respectively, rBPI(23), LPS, and LPS-rBPI(23) complexes was assessed. Following incubation with rBPI(23), LPS, and LPS-rBPI(23) complexes, complex levels were generated at levels comparable to those observed in the buffer control. The rapid vasodilatation by endotoxin administered concomitantly with rBPI(23) is not mediated by complement or contact system activation. The early vasodilatation is compensated by an increase in cardiac output, which therefore does not result in arterial hypotension. The monitoring of continuous cardiac output allows for the detection of rapid effects on systemic flow and conductance that go unnoticed in a recording of arterial pressure.