Weiner D L, Kuppermann N, Saladino R A, Thompson C M, Novitsky T J, Siber G R, Fleisher G R
Department of Medicine, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Crit Care Med. 1996 Sep;24(9):1514-7. doi: 10.1097/00003246-199609000-00014.
To test the efficacy of a recombinant endotoxin neutralizing protein as compared with saline in rats with Escherichia coli sepsis.
Prospective, controlled animal trial.
Hospital animal research laboratory.
Male Wistar rats challenged with intraperitoneal E. coli, O18ac K1, and treated 1 hr later with ceftriaxone and gentamicin.
Recombinant endotoxin neutralizing protein, 50 mg/kg, was administered to rats 1, 2, or 3 hrs after E. coli challenge; saline was administered to control animals.
Quantitative bacteremia, 1 hr after challenge and before antibiotic administration, was not significantly different between treatment groups (range geometric mean 451 to 621 colony-forming units [cfu]/mL). The endotoxin concentration, measured immediately before recombinant endotoxin neutralizing protein administration, was significantly higher in animals sampled and treated at 2 hrs (geometric mean 260 EU/mL; 95% confidence interval 140 to 480 EU/mL), or 3 hrs (geometric mean 697 EU/mL; 95% confidence interval 307 to 1585 EU/mL) after E. coli challenge, compared with animals sampled and treated at 1 hr (geometric mean 17 EU/mL; 95% confidence interval 7 to 69 EU/ mL). Survival rate was significantly greater in rats treated with recombinant endotoxin neutralizing protein at 1 hr (23/27; p < .001) or 2 hrs (8/30; p < .01) after E. coli challenge than in controls (1/32).
Administration of recombinant endotoxin neutralizing protein delayed up to 2 hrs after challenge with E. coli improves survival in antibiotic-treated rats with Gram-negative sepsis.
在患有大肠杆菌败血症的大鼠中，测试重组内毒素中和蛋白与生理盐水相比的疗效。
前瞻性对照动物试验。
医院动物研究实验室。
雄性Wistar大鼠，经腹腔注射大肠杆菌O18ac K1进行攻击，1小时后用头孢曲松和庆大霉素治疗。
在大肠杆菌攻击后1、2或3小时，给大鼠注射50mg/kg重组内毒素中和蛋白；给对照动物注射生理盐水。
攻击后1小时且在给予抗生素之前，各治疗组间的定量菌血症无显著差异（几何平均值范围为451至621菌落形成单位[cfu]/mL）。在给予重组内毒素中和蛋白之前立即测量的内毒素浓度，在大肠杆菌攻击后2小时（几何平均值260 EU/mL；95%置信区间140至480 EU/mL）或3小时（几何平均值697 EU/mL；95%置信区间307至1585 EU/mL）采样并治疗的动物中，显著高于在1小时（几何平均值17 EU/mL；95%置信区间7至69 EU/mL）采样并治疗的动物。在大肠杆菌攻击后1小时（23/27；p<.001）或2小时（8/30；p<.01）接受重组内毒素中和蛋白治疗的大鼠的存活率显著高于对照组（1/32）。
在大肠杆菌攻击后长达2小时给予重组内毒素中和蛋白，可提高接受抗生素治疗的革兰氏阴性败血症大鼠的存活率。
