Rackow E C, Astiz M E, Kim Y B, Weil M H
Department of Medicine, University of Health Sciences, Chicago Medical School, IL 60064.
J Lab Clin Med. 1989 Jan;113(1):112-7.
Monophosphoryl lipid A (MPL) is a "nontoxic" derivative of lipid A. We hypothesized that, because of the structural similarity between MPL and the lipid A portion of lipopolysaccharide (a "toxic" moiety of endotoxin), hemodynamic events occurring during endotoxemia could be attenuated by administration of MPL. Lipopolysaccharide (LPS) from Salmonella minnesota wild type S and MPL from S. minnesota R595 were used for the study. Fifteen Sprague-Dawley rats were randomized to receive either (1) 0.50 mg LPS per 100 gm body weight intravenously, (2) 0.50 mg MPL per 100 gm body weight intravenously, or (3) 0.5 mg MPL per 100 gm body weight intravenously followed in 15 minutes by 0.50 mg LPS per 100 gm body weight intravenously. Arterial pressure, thermodilution cardiac output, and central venous oxygen saturation were measured before and 30 and 60 minutes after LPS administration. In LPS-treated animals, cardiac output decreased from 448 +/- 28 ml/kg/min to 336 +/- 15 ml/kg/min (p less than 0.02), and central venous oxygen saturation decreased from 71% +/- 1% to 62% +/- 2% (p less than 0.05). Mean arterial pressure decreased from 134 +/- 5 mm Hg to 90 +/- 6 mm Hg (p less than 0.01). In MPL-treated and MPL + LPS-treated animals, no significant changes were observed in cardiac output, central venous oxygen saturation, or arterial pressure. These data indicate that MPL is not associated with the adverse cardiovascular responses observed after LPS administration. Furthermore, administration of MPL blocks the development of acute circulatory failure during endotoxemia.
单磷酰脂质A（MPL）是脂质A的一种“无毒”衍生物。我们推测，由于MPL与脂多糖的脂质A部分（内毒素的“有毒”部分）结构相似，在内毒素血症期间发生的血流动力学事件可通过给予MPL而减轻。本研究使用了来自明尼苏达沙门氏菌野生型S的脂多糖（LPS）和来自明尼苏达沙门氏菌R595的MPL。15只Sprague-Dawley大鼠被随机分为三组，分别接受：（1）每100克体重静脉注射0.50毫克LPS；（2）每100克体重静脉注射0.50毫克MPL；或（3）每100克体重静脉注射0.5毫克MPL，15分钟后再每100克体重静脉注射0.50毫克LPS。在给予LPS前以及给药后30分钟和60分钟测量动脉压、热稀释心输出量和中心静脉血氧饱和度。在LPS处理的动物中，心输出量从448±28毫升/千克/分钟降至336±15毫升/千克/分钟（p<0.02），中心静脉血氧饱和度从71%±1%降至62%±2%（p<0.05）。平均动脉压从134±5毫米汞柱降至90±6毫米汞柱（p<0.01）。在MPL处理组和MPL+LPS处理组动物中，心输出量、中心静脉血氧饱和度或动脉压均未观察到显著变化。这些数据表明，MPL与LPS给药后观察到的不良心血管反应无关。此外，给予MPL可阻断内毒素血症期间急性循环衰竭的发生。
