Carpati C M, Astiz M E, Saha D C, Rackow E C
St. Vincent's Hospital and Medical Center, New York Medical College, NY 10011.
Crit Care Med. 1993 May;21(5):753-8. doi: 10.1097/00003246-199305000-00020.
To examine the hemodynamic effects of diphosphoryl lipid A from Rhodopseudomonas sphaeroides and to examine the ability of this substance to induce tolerance to endotoxic shock.
Randomized, prospective, controlled study comparing the hemodynamic actions of R. sphaeroides diphosphoryl lipid A to those effects of lipopolysaccharide form Salmonella minnesota, followed by a prospective, randomized, controlled study comparing pretreatment with R. sphaeroides diphosphoryl lipid A and phosphate-buffered saline in the induction of tolerance to endotoxic shock.
Laboratory of the Section of Critical Care Medicine at a University Hospital.
Male Sprague-Dawley rats.
Eight rats were randomized to receive intravenous R. sphaeroides diphosphoryl lipid A, 0.5 mg/100 g body weight or S. minnesota lipopolysaccharide, 0.5 mg/100 g body weight. Ten rats were then randomized to receive R. sphaeroides diphosphoryl lipid A, 0.5 mg/100 g body weight, or phosphate-buffered saline intravenously 48 hrs before receiving S. minnesota lipopolysaccharide, 5 mg/100 g body weight, by intravenous infusion.
Cardiac index was significantly decreased from baseline in rats treated with lipopolysaccharide; there was no significant change in the R. sphaeroides diphosphoryl lipid A group. Peak circulating tumor necrosis factor (TNF) concentrations in the lipopolysaccharide-treated rats were higher than in R. sphaeroides diphosphoryl lipid A-treated rats (3.1 +/- 1.0 vs. 1.5 +/- 0.4 ng/mL). R. sphaeroides diphosphoryl lipid A significantly attenuated lipopolysaccharide-induced changes in mean arterial pressure and cardiac index. At baseline, there was no significant difference in serum TNF concentrations between rats pretreated with R. sphaeroides diphosphoryl lipid A and those rats pretreated with phosphate-buffered saline. TNF levels peaked at 1 hr post-lipopolysaccharide infusion at 4.3 +/- 0.6 ng/mL in the phosphate-buffered saline group and at 2.0 +/- 0.5 ng/mL in the R. sphaeroides diphosphoryl lipid A group (p < .02). Four of five rats pretreated with R. sphaeroides diphosphoryl lipid A survived endotoxic shock, whereas none of the phosphate-buffered saline-pretreated rats survived (p = .05).
These observations are consistent with previous reports of the limited toxic effects of R. sphaeroides diphosphoryl lipid A and suggest that this molecule retains the ability to induce tolerance to endotoxic shock.
研究球形红假单胞菌二磷酸脂质A的血流动力学效应，并考察该物质诱导对内毒素休克耐受性的能力。
随机、前瞻性、对照研究，比较球形红假单胞菌二磷酸脂质A与明尼苏达沙门氏菌脂多糖的血流动力学作用，随后进行前瞻性、随机、对照研究，比较球形红假单胞菌二磷酸脂质A预处理和磷酸盐缓冲盐水预处理对内毒素休克耐受性诱导的影响。
大学医院重症医学科实验室。
雄性Sprague-Dawley大鼠。
8只大鼠随机接受静脉注射球形红假单胞菌二磷酸脂质A（0.5 mg/100 g体重）或明尼苏达沙门氏菌脂多糖（0.5 mg/100 g体重）。然后，10只大鼠在静脉输注5 mg/100 g体重的明尼苏达沙门氏菌脂多糖前48小时，随机接受静脉注射球形红假单胞菌二磷酸脂质A（0.5 mg/100 g体重）或磷酸盐缓冲盐水。
脂多糖处理的大鼠心脏指数较基线显著降低；球形红假单胞菌二磷酸脂质A组无显著变化。脂多糖处理的大鼠循环肿瘤坏死因子（TNF）峰值浓度高于球形红假单胞菌二磷酸脂质A处理的大鼠（3.1±1.0 vs. 1.5±0.4 ng/mL）。球形红假单胞菌二磷酸脂质A显著减轻脂多糖诱导的平均动脉压和心脏指数变化。基线时，球形红假单胞菌二磷酸脂质A预处理的大鼠与磷酸盐缓冲盐水预处理的大鼠血清TNF浓度无显著差异。脂多糖输注后1小时，磷酸盐缓冲盐水组TNF水平峰值为4.3±0.6 ng/mL，球形红假单胞菌二磷酸脂质A组为2.0±0.5 ng/mL（p<0.02）。5只接受球形红假单胞菌二磷酸脂质A预处理的大鼠中有4只在内毒素休克中存活，而磷酸盐缓冲盐水预处理的大鼠无一存活（p=0.05）。
这些观察结果与先前关于球形红假单胞菌二磷酸脂质A毒性作用有限的报道一致，并表明该分子保留了诱导对内毒素休克耐受性的能力。
