Prophylactic treatment with an aerosolized corticosteroid liposome in a porcine model of early ARDS induced by endotoxaemia.

Acta chirurgica Scandinavica Pub Date : 1990-06-01
P E Forsgren, J A Modig, C M Dahlbäck, B I Axelsson
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Abstract

The effects of prophylactic treatment with an aerosolized corticosteroid liposome (CSL) in high dose were evaluated in a porcine model of early Adult Respiratory Distress Syndrome (ARDS) induced by endotoxaemia. Intermittent positive pressure ventilated (IPPV) pigs under chlormethiazole anaesthesia were infused with E. coli endotoxin (18 micrograms.kg-1.h-1) over 4 h. Eight animals served as controls and were pretreated with aerosolized placebo liposomes, either 15 min or 2 h, before start of the endotoxin infusion. Eight animals were pretreated with CSL in aerosolized form 15 min before start of endotoxin, and eight animals were pretreated 2 h before start of endotoxin. Pretreatment with CSL, both 15 min and 2 h before endotoxin, modified and partly counteracted the late endotoxin-induced impairment in expiratory resistance (EXPres), dynamic compliance (Cdyn) and mean pulmonary artery pressure (MPAP). The administration of CSL did not seem to have a restrictive influence on the endogenous cortisol production estimated by repeated measurements of serum cortisol levels. These results indicate that CSL, administered prophylactically in an aerosolized form to the lung, might be valuable as a modulator without systemic side effects in regard to some of the endotoxin-induced pulmonary impairments seen in this experimental model of early ARDS.

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雾化皮质类固醇脂质体预防内毒素血症引起的早期急性呼吸窘迫综合征猪模型。
在猪内毒素血症引起的早期成人呼吸窘迫综合征(ARDS)模型中,研究了高剂量皮质类固醇脂质体(CSL)雾化预防治疗的效果。间歇性正压通气(IPPV)猪在氯甲咪唑麻醉下注射大肠杆菌内毒素(18微克。kg-1.h-1) 4小时。8只动物作为对照,在内毒素输注开始前15分钟或2小时用雾化安慰剂脂质体预处理。8只动物在内毒素开始前15 min以雾化形式用CSL预处理,8只动物在内毒素开始前2 h预处理。在内毒素出现前15分钟和2小时,用CSL进行预处理,可以改善并部分抵消内毒素引起的呼气阻力(EXPres)、动态顺应性(Cdyn)和平均肺动脉压(MPAP)的损伤。通过反复测量血清皮质醇水平估计,CSL的施用似乎对内源性皮质醇产生没有限制性影响。这些结果表明,在这个早期ARDS实验模型中看到的一些内毒素诱导的肺损伤中,CSL以雾化形式预防性地给予肺,可能是一种有价值的无系统性副作用的调节剂。
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