Leeper-Woodford S K, Carey D, Byrne K, Walsh C, Fisher B, Sugerman H J, Fowler A A
Department of Medicine, Virginia Commonwealth University/Medical College of Virginia, Richmond, USA.
Shock. 1998 Feb;9(2):89-94. doi: 10.1097/00024382-199802000-00003.
Tumor necrosis factor (TNF) may be a major endogenous mediator of sepsis-induced acute organ injury. We proposed that treatment of septic pigs with the combined agents ibuprofen, a cyclooxygenase inhibitor, and histamine receptor antagonists, cimetidine (H2 antagonist) and diphenhydramine (H1 antagonist) would result in lower circulating levels of TNF and decreased parameters of sepsis-induced injury in these animals. To test this, plasma TNF activity, cardiac index, systemic and pulmonary arterial pressures, arterial PO2 and bronchoalveolar lavage protein content were monitored for 300 min in four groups of anesthetized pigs: saline-infused control pigs (n = 4); pigs infused for 60 min with Pseudomonas aeruginosa (5 x 10(8) organisms/mL, .3 mL/20 kg/min) (n = 5) and pigs infused for 60 min with P. aeruginosa plus ibuprofen (12.5 mg/kg) alone (n = 4) or ibuprofen plus cimetidine (150 mg) and diphenhydramine (30 mg/kg) at 0 and 120 min (CID, n = 4). Within 60 min, pigs infused with P. aeruginosa exhibited increased plasma TNF activity (>8-fold increase in ng/mL TNF; L929 cytolysis assay) and showed alterations in all hemodynamic and pulmonary parameters. Ibuprofen or CID administration in the septic pigs decreased peak TNF activity by 4.6 and 10.2 ng/mL, respectively, and CID treatment was correlated with better attenuation of certain sepsis-induced alterations. These results show that CID treatment attenuates sepsis-induced injury and that this is correlated with reduced plasma TNF activity in a porcine model of sepsis-induced acute organ injury.
肿瘤坏死因子（TNF）可能是脓毒症诱导的急性器官损伤的主要内源性介质。我们提出，用联合药物治疗脓毒症猪，即环氧化酶抑制剂布洛芬以及组胺受体拮抗剂西咪替丁（H2拮抗剂）和苯海拉明（H1拮抗剂），会使这些动物体内TNF的循环水平降低，并使脓毒症诱导的损伤参数减少。为了验证这一点，在四组麻醉猪中监测了300分钟的血浆TNF活性、心脏指数、体循环和肺动脉压、动脉血氧分压以及支气管肺泡灌洗蛋白含量：输注生理盐水的对照猪（n = 4）；输注铜绿假单胞菌60分钟的猪（5×10⁸个菌/mL，0.3 mL/20 kg/min）（n = 5），以及输注铜绿假单胞菌加单独的布洛芬（12.5 mg/kg）60分钟的猪（n = 4），或在0和120分钟时输注布洛芬加西咪替丁（150 mg）和苯海拉明（30 mg/kg）的猪（CID组，n = 4）。在60分钟内，输注铜绿假单胞菌的猪血浆TNF活性增加（TNF的ng/mL增加超过8倍；L929细胞溶解试验），并且所有血流动力学和肺部参数均出现改变。在脓毒症猪中给予布洛芬或CID分别使TNF活性峰值降低4.6和10.2 ng/mL，并且CID治疗与某些脓毒症诱导的改变的更好缓解相关。这些结果表明，在脓毒症诱导的急性器官损伤的猪模型中，CID治疗减轻了脓毒症诱导的损伤，并且这与血浆TNF活性降低相关。
