Yoshizawa M, Ohtake K, Kubota T
Department of ICU.CCU, Jichi Medical School.
Masui. 1991 Apr;40(4):605-10.
Intravenous bolus administration of purified endotoxin (ET) is one of the most popular methods of producing experimental ET shock. In an attempt to evaluate the dose of ET in these experimental models, the kinetics of ET was assessed in various doses (1-0.002 mg.kg-1), and dose response study was performed, measuring chronological changes in hemodynamic (mean arterial pressure & cardiac output) and hematological (leucocyte & platelet counts) parameters. It was demonstrated that plasma ET concentrations were sustained extraordinarily high (greater than 5000 pg.ml-1) in doses of 0.2-1 mg.kg-1 during the observation period of several hours, while they were measurable in doses of 0.02 and 0.002 mg.kg-1, showing a biphasic decrease pattern after ET administration. In particular, plasma ET levels of low dose group (0.002 mg.kg-1) were similar to those of clinical gram negative septic patients. We conclude that the empirically used ET doses of more than 1 mg.kg-1 produce extremely severe endotoxemia and that milder degree of ET shock models produced by low dose of ET (0.002 mg.kg-1) would be more applicable for a pathophysiological study of ET shock.
静脉推注纯化内毒素（ET）是产生实验性ET休克最常用的方法之一。为了评估这些实验模型中ET的剂量，我们评估了不同剂量（1 - 0.002 mg.kg-1）ET的动力学，并进行了剂量反应研究，测量了血流动力学（平均动脉压和心输出量）和血液学（白细胞和血小板计数）参数随时间的变化。结果表明，在数小时的观察期内，0.2 - 1 mg.kg-1剂量的血浆ET浓度持续异常高（大于5000 pg.ml-1），而在0.02和0.002 mg.kg-1剂量下可检测到，给药后呈现双相下降模式。特别是，低剂量组（0.002 mg.kg-1）的血浆ET水平与临床革兰氏阴性败血症患者相似。我们得出结论，经验性使用超过1 mg.kg-1的ET剂量会产生极其严重的内毒素血症，而低剂量ET（0.002 mg.kg-1）产生的较轻程度的ET休克模型更适用于ET休克的病理生理学研究。
