Histamine receptor antagonists, cyclooxygenase blockade, and tumor necrosis factor during acute septic insult.
Histamine receptor antagonists, cyclooxygenase blockade, and tumor necrosis factor during acute septic insult.
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急性脓毒症期间的组胺受体拮抗剂、环氧合酶阻断剂和肿瘤坏死因子。
DOI：
10.1097/00024382-199802000-00003
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Fowler,AA
中科院分区：
文献类型：
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作者：
Leeper-Woodford,SK;Carey,D;Byrne,K;Walsh,C;Fisher,B;Sugerman,HJ;Fowler,AA
肿瘤坏死因子（TNF）可能是脓毒症引起的急性器官损伤的主要内源性介质。我们提出，用布洛芬（环氧化酶抑制剂）和组胺受体拮抗剂西咪替丁（h2拮抗剂）和苯海拉明（h1拮抗剂）联合治疗败血症猪，可以降低这些动物的循环TNF水平，降低败血症引起的损伤参数。为了验证这一点，在麻醉的四组猪中监测300分钟血浆TNF活性、心脏指数、全身和肺动脉压、动脉Po 2和支气管肺泡灌洗液蛋白含量：对照组猪（n= 4）；铜绿假单胞菌灌胃60分钟（5 × 108个/mL）。P.铜绿假单胞菌加布洛芬（12.5 mg/kg） （n= 4）或布洛芬加西咪替丁（150 mg）和苯海拉明（30 mg/kg）分别在0和120 min （CID, n= 4）输注60 min （n= 4）。在60分钟内，注射铜绿假单胞菌的猪表现出血浆TNF活性增加（ng/mL TNF增加8倍；L929细胞溶解测定），并显示出所有血流动力学和肺参数的改变。布洛芬或CID分别使败血症猪的TNF活性峰值降低4.6和10.2 ng/mL， CID治疗与某些败血症诱导的改变的更好衰减相关。这些结果表明，CID治疗减轻败血症诱导的损伤，这与败血症诱导的急性器官损伤猪模型中血浆TNF活性降低有关。
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 cycloox-ygenase inhibitor, and histamine receptor antagonists, cimetidine (H 2 antagonist) and diphenhydramine (H 1 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 Po 2 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 108 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.