Carbon monoxide pretreatment prevents respiratory derangement and ameliorates hyperacute endotoxic shock in pigs
Carbon monoxide pretreatment prevents respiratory derangement and ameliorates hyperacute endotoxic shock in pigs
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DOI：
10.1096/fj.05-3782fje
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发表时间：
2005-10-01
期刊：
影响因子：
4.8
通讯作者：
Clement, MG
中科院分区：
文献类型：
--
作者：
Mazzola, S;Forni, M;Clement, MG
内毒素休克是重症监护病房最重要的死亡原因之一，其特征是肺动脉高压、全身性低血压、心力衰竭、广泛的内皮激活/损伤以及最终导致弥散性血管内凝血和多器官系统衰竭的凝血。过去几年，对啮齿动物的研究表明，低浓度的一氧化碳 (CO) 对多种疾病/病症具有有效的治疗作用。在这项研究中，我们在临床相关、特征明确的 LPS 诱导的猪急性肺损伤模型中施用 CO（我们的预处理之一是 250 ppm）。仅用吸入 CO 进行预处理可显着改善内毒素休克引起的几种急性病理变化。在肺生理学方面，CO预处理纠正了LPS引起的阻力和顺应性变化，改善了肺气体交换的紊乱。在凝血和炎症方面，CO 减少了弥散性血管内凝血的发展，并完全抑制了 LPS 响应的促炎性 IL-1β 的血清水平，同时增强了抗炎细胞因子 IL-10。此外，一氧化碳的作用可以减缓肾和肝功能的恶化，这表明对与内毒素休克相关的终末器官损伤具有有益的作用。最后，CO 预处理可防止 LPS 诱导的肺内皮细胞 ICAM 表达，并抑制肺实质上的白细胞边缘化。
Endotoxic shock, one of the most prominent causes of mortality in intensive care units, is characterized by pulmonary hypertension, systemic hypotension, heart failure, widespread endothelial activation/ injury, and clotting culminating in disseminated intravascular coagulation and multi-organ system failure. In the last few years, studies in rodents have shown that administration of low concentrations of carbon monoxide ( CO) exerts potent therapeutic effects in a variety of diseases/disorders. In this study, we have administered CO ( one our pretreatment at 250 ppm) in a clinically relevant, well-characterized model of LPS-induced acute lung injury in pigs. Pretreatment only with inhaled CO significantly ameliorated several of the acute pathological changes induced by endotoxic shock. In terms of lung physiology, CO pretreatment corrected the LPS-induced changes in resistance and compliance and improved the derangement in pulmonary gas exchange. In terms of coagulation and inflammation, CO reduced the development of disseminated intravascular coagulation and completely suppressed serum levels of the proinflammatory IL-1 beta in response to LPS, while augmenting the anti-inflammatory cytokine IL-10. Moreover, the effects of CO blunted the deterioration of kidney and liver function, suggesting a beneficial effect in terms of end organ damage associated with endotoxic shock. Lastly, CO pretreatment prevents LPS-induced ICAM expression on lung endothelium and inhibits leukocyte marginalization on lung parenchyma.