Delayed treatment with recombinant human tissue factor pathway inhibitor improves survival in rabbits with gram-negative peritonitis
Delayed treatment with recombinant human tissue factor pathway inhibitor improves survival in rabbits with gram-negative peritonitis
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DOI：
10.1086/514246
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发表时间：
1998-03-01
影响因子：
6.4
通讯作者：
Fink, MP
中科院分区：
文献类型：
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作者：
Camerota, AJ;Creasey, AA;Fink, MP
为了确定外源性凝血途径抑制剂重组人组织因子途径抑制剂（TFPI）是否能提高临床相关革兰氏阴性脓毒症模型的存活率，研究人员给家兔腹腔注射含有血红蛋白（40 μ g/mL）、猪粘蛋白（150 μ g/mL）和活菌大肠杆菌O18:K1 （1.0 +/- 0.5 × 10(5) cfu/kg）的混悬液。在诱导腹膜炎4小时后给予庆大霉素（5 mg/kg每12 h，共5次）治疗。同一时间点，随机取家兔分别给予24 h载药或三种不同剂量的TFPI之一，治疗组7天生存率，与对照组比较，显著性如下：对照组，20只中有1只；TFPILOW剂量先0.1 mg/kg，再1 mu g/kg/min， 3 / 12 (P = 0.14)；TFPIMID剂量，先0.5 mg/kg，再5 μ g/kg/min， 7 / 12 (P = 0.002)；TFPI高剂量（10 mg/kg，然后是10 μ g/kg/min）， 13例中有4例（P = .04），因此，延迟TFPI治疗可提高脓毒症家兔的存活率。
To determine whether treatment with recombinant human tissue factor pathway inhibitor (TFPI), an inhibitor of the extrinsic coagulation pathway, can improve survival in a clinically relevant model of gram-negative sepsis, rabbits were given an intraperitoneal inoculation of a suspension containing hemoglobin (40 mu g/mL), porcine mucin (150 mu g/mL), and viable Escherichia coli O18:K1 (1.0 +/- 0.5 x 10(5) cfu/kg). Treatment with gentamicin (5 mg/kg every 12 h for five doses) was instituted 4 h after induction of peritonitis. At the same time point, rabbits were randomized to receive a 24-h infusion of vehicle or one of three different doses of TFPI, Treatment groups, 7-day survival rates, and significance versus control were as follows: control, 1 of 20; TFPILOW DOSE (0.1 mg/kg, then 1 mu g/kg/min), 3 of 12 (P = .14); TFPIMID DOSE, (0.5 mg/kg, then 5 mu g/kg/min), 7 of 12 (P = .002); TFPIHIGH DOSE (10 mg/kg, then 10 mu g/kg/min), 4 of 13 (P = .04), Thus, delayed treatment with TFPI improves survival in septic rabbits.