Nakayama M, Hasegawa N, Oka Y, Lutzke B, McCall J M, Raffin T A
Division of Pulmonary and Critical Care Medicine, Stanford University Medical Center, CA 94305-5236, USA.
Crit Care Med. 1998 Mar;26(3):538-47. doi: 10.1097/00003246-199803000-00029.
To assess the effects of the lazaroid, tirilazad mesylate, a potent lipid peroxidation inhibitor, in an animal model of Pseudomonas sepsis.
Comparison of four experimental groups: a) saline control; b) Pseudomonas sepsis control; c) tirilazad mesylate control; and d) sepsis with tirilazad mesylate pre treatment.
University animal laboratory.
Hanford minipigs (20 to 25 kg), anesthetized with pentobarbital and mechanically ventilated on an FIO2 of 0.4.
Sepsis was induced by infusing Pseudomonas aeruginosa at 1 x 10(6) colony-forming units/kg/min over 120 mins. The tirilazad mesylate-treated group received a 5-mg/kg bolus 30 mins before, and a 3-mg/kg bolus 3 hrs after, the onset of sepsis. Hemodynamics, PaO2, and neutrophil counts were measured for 6 hrs. Thiobarbituric acid reactive material (TBARM) in tissue (lung, liver, and intestine), lung wet/dry weight ratio, lung myeloperoxidase activity, plasma tumor necrosis factor (TNF)-alpha concentrations, protein content, and percent neutrophils in bronchoalveolar lavage fluid were evaluated at the time the animals were killed (6 hrs).
Sepsis induced significant systemic hypotension, pulmonary hypertension, hypoxemia, and neutropenia. Sepsis also significantly increased TBARM content, lung wet/dry weight ratio, myeloperoxidase activity, plasma TNF-alpha concentrations, and bronchoalveolar lavage neutrophil percentage. Treatment with tirilazad mesylate significantly attenuated hypoxemia and decreased TBARM content, lung wet/dry weight ratio, myeloperoxidase activity, bronchoalveolar lavage protein, and bronchoalveolar lavage neutrophil percentage, but did not affect sepsis-induced hemodynamics, including systemic hypotension and pulmonary hypertension, plasma TNF-alpha concentrations, or neutropenia.
Pretreatment with the tirilazad mesylate did not change P. aeruginosa sepsis-induced hemodynamic consequences. However, tirilazad mesylate attenuated sepsis-induced acute lung injury.
评估强效脂质过氧化抑制剂甲磺酰替拉扎德（lazaroid，tirilazad mesylate）在铜绿假单胞菌败血症动物模型中的作用。
四个实验组的比较：a）生理盐水对照组；b）铜绿假单胞菌败血症对照组；c）甲磺酰替拉扎德对照组；d）甲磺酰替拉扎德预处理的败血症组。
大学动物实验室。
汉福德小型猪（20至25千克），用戊巴比妥麻醉，并在0.4的吸入氧分数下进行机械通气。
通过在120分钟内以1×10(6) 菌落形成单位/千克/分钟的速度输注铜绿假单胞菌诱导败血症。甲磺酰替拉扎德治疗组在败血症发作前30分钟接受5毫克/千克的推注，并在败血症发作后3小时接受3毫克/千克的推注。测量血流动力学、动脉血氧分压（PaO2）和中性粒细胞计数6小时。在动物处死时（6小时）评估组织（肺、肝和肠）中的硫代巴比妥酸反应物质（TBARM）、肺湿/干重比、肺髓过氧化物酶活性、血浆肿瘤坏死因子（TNF）-α浓度、蛋白质含量以及支气管肺泡灌洗液中的中性粒细胞百分比。
败血症导致显著的全身性低血压、肺动脉高压、低氧血症和中性粒细胞减少。败血症还显著增加了TBARM含量、肺湿/干重比、髓过氧化物酶活性、血浆TNF-α浓度以及支气管肺泡灌洗中性粒细胞百分比。甲磺酰替拉扎德治疗显著减轻了低氧血症，并降低了TBARM含量、肺湿/干重比、髓过氧化物酶活性、支气管肺泡灌洗蛋白和支气管肺泡灌洗中性粒细胞百分比，但不影响败血症诱导的血流动力学，包括全身性低血压和肺动脉高压、血浆TNF-α浓度或中性粒细胞减少。
甲磺酰替拉扎德预处理并未改变铜绿假单胞菌败血症诱导的血流动力学后果。然而，甲磺酰替拉扎德减轻了败血症诱导的急性肺损伤。
