TNF-alpha and the pathophysiology of endotoxin-induced acute respiratory failure in sheep.
TNF-alpha and the pathophysiology of endotoxin-induced acute respiratory failure in sheep.
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TNF-α 和内毒素诱导的绵羊急性呼吸衰竭的病理生理学。
DOI：
10.1152/jappl.1996.80.2.564
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Gee,MH
中科院分区：
文献类型：
--
作者：
Perkowski,SZ;Sloane,PJ;SpathJr,JA;Elsasser,TH;Fisher,JK;Gee,MH
我们研究了清醒绵羊在长期内毒素血症期间心血管和肺功能的变化。患有慢性肺淋巴瘘的绵羊接受了12小时的大肠杆菌内毒素（10 ng x kg-1 x min-1）输注，并允许恢复12小时。停止支持治疗。无容量支持的长期内毒素血症导致全身性低血压，与心输出量减少和全身血管阻力增加、肺动脉高压和急性肺损伤伴进行性呼吸衰竭相关。血浆肿瘤坏死因子-α（TNF-α）浓度一过性升高。持续性肺动脉高压和肺血管和全身血管阻力增加导致34只绵羊中有9只（26%）结局不佳。血浆TNF-α浓度显着更大的幸存者持续肺动脉高压和非幸存的羊比幸存的羊没有肺动脉高压。内毒素（1 ng/ml）增加体外中性粒细胞TNF-α的表达。白细胞介素-6的加入阻止了这种反应。TNF-α的合成和释放可能是影响持续性肺动脉高压和进行性呼吸衰竭伴内毒素血症发展的重要近端事件。白细胞介素-6可能有助于TNF-α反应的阶段性。
We studied changes in cardiovascular and pulmonary function during prolonged endotoxemia in conscious sheep. Sheep with chronic lung lymph fistulas received a 12-h infusion of Escherichia coli endotoxin (10 ng x kg-1 x min-1) and allowed to recover for 12 h. Supportive therapies were withheld. Prolonged endotoxemia without volume support caused systemic hypotension associated with reduced cardiac output and increased systemic vascular resistance, pulmonary hypertension, and acute lung injury with progressive respiratory failure. Plasma tumor necrosis factor-alpha (TNF-alpha) concentrations increased transiently. Sustained pulmonary hypertension and increased pulmonary and systemic vascular resistances contributed to a poor outcome in 9 of 34 sheep (26%). Plasma TNF-alpha concentrations were significantly greater in survivors with sustained pulmonary hypertension and in nonsurviving sheep than in surviving sheep without pulmonary hypertension. Endotoxin (1 ng/ml) increased neutrophil expression of TNF-alpha in vitro. Addition of interleukin-6 prevented this response. Synthesis and release of TNF-alpha may be an important proximal event influencing the development of sustained pulmonary hypertension and progressive respiratory failure with endotoxemia. Interleukin-6 may contribute to the phasic nature of the TNF-alpha response.