Etanercept reduces late endotoxin-induced pulmonary hypertension in the pig
Etanercept reduces late endotoxin-induced pulmonary hypertension in the pig
复制标题
DOI：
10.1089/jir.2006.26.661
复制
发表时间：
2006-09-01
影响因子：
2.3
通讯作者：
Eriksson, M.
中科院分区：
文献类型：
--
作者：
Mutschler, D.;Wikstrom, G.;Eriksson, M.
为了评估依那西普（一种肿瘤坏死因子（TNF）阻断剂）是否可以对抗内毒素血症性休克时的血流动力学恶化，我们设计了一项前瞻性、随机安慰剂对照试验，平行组包括13只接受全身麻醉的10 - 14周龄猪。在开始4小时内毒素连续输注前1小时，对5头猪给予25 mg依那西普。另5头猪在开始连续输注内毒素4 h前1 h给予相应体积的生理盐水。在开始4小时连续输注生理盐水前1小时，对3头猪给予25 mg依那西普。在1小时的内毒素血症，平均肺动脉压（MPAP）和肺血管阻力指数（PVRI）增加相同的两组猪接受内毒素。此后，观察到两种截然不同的血流动力学模式。与对照组相比，TNF阻断的猪显示出显著较低的MPAP和PVRI。在依那西普治疗的内毒素血症猪中，舒张期二尖瓣流入的多普勒分析显示2 h时E/A比值显著增加（早期二尖瓣波流入除以心房波）。TNF阻断剂依那西普使猪内毒素诱导的感染性休克的两个血流动力学特征正常化：（1）持续性肺动脉高压和（2）舒张功能障碍。
To evaluate whether etanercept, a tumor necrosis factor (TNF)-blocking agent, may counteract hemodynamic deterioration in endotoxemic shock, we designed a prospective, randomized placebo-controlled trial with parallel groups, consisting of 13 pigs aged 10 - 14 weeks receiving general anesthesia. Five pigs were given 25 mg of etanercept, 1 h before the start of a 4-h continuous infusion of endotoxin. Another 5 pigs were given the corresponding volume of saline, 1 h before the start of a 4-h continuous infusion of endotoxin. Three pigs were given 25 mg of etanercept, 1 hr before the start of a 4-h continuous infusion of saline. At 1 h of endotoxemia, mean pulmonary arterial pressure (MPAP) and pulmonary vascular resistance index (PVRI) increased identically in both groups of pigs receiving endotoxin. Thereafter, two distinct different patterns in hemodynamics were observed. TNF-blocked pigs showed significantly lower MPAP and PVRI compared to controls. In the etanercept-treated endotoxemic pigs, Doppler analysis of the diastolic mitral inflow demonstrated a significantly increased E/A-ratio (early mitral wave inflow was divided by the atrial wave) at 2 h. The TNF-blocking agent etanercept normalized two hemodynamic features of endotoxin-induced septic shock in pigs: (1) the sustained pulmonary hypertension and (2) diastolic dysfunction.