Shah N S, Nakayama D K, Jacob T D, Nishio I, Imai T, Billiar T R, Exler R, Yousem S A, Motoyama E K, Peitzman A B
Department of Pediatric Surgery, Children's Hospital of Pittsburgh, USA.
Crit Care Med. 1997 Jan;25(1):153-8. doi: 10.1097/00003246-199701000-00028.
To assess the efficacy of inhaled nitric oxide in improving pulmonary hypertension and gas exchange following oleic acid-induced acute lung injury.
Prospective, pharmacologic study.
Surgical research laboratory at the University of Pittsburgh, Pittsburgh, PA.
Instrumented, intubated pigs weighing 16 to 27 kg.
Intravenous oleic acid and inhaled nitric oxide.
All pigs treated with intravenous oleic acid (0.11 mL/kg) developed a severe lung injury with pulmonary hypertension, accompanied by impaired oxygenation, intrapulmonary shunting, and increased extravascular lung water (p < .05 compared with baseline). Following nitric oxide inhalation, although pulmonary hypertension decreased in a dose-dependent fashion, no amelioration in pulmonary gas exchange was observed, as reflected by PaO2 and intrapulmonary shunt. Plasma nitrite and nitrate concentrations, the stable end products of nitric oxide metabolism, did not increase following nitric oxide exposure in this model of severe lung injury.
The effect of inhaled nitric oxide, restricted to relieving pulmonary vasoconstriction in this model of lung injury, may have limited benefit in improving pulmonary gas exchange when diffusion is impaired by severe lung injury and inflammatory thickening of the alveolar-capillary barrier. Nitric oxide inhalation may have better results when used at an earlier, less severe stage of acute lung injury.
评估吸入一氧化氮对油酸诱导的急性肺损伤后改善肺动脉高压和气体交换的疗效。
前瞻性药理学研究。
宾夕法尼亚州匹兹堡市匹兹堡大学外科研究实验室。
体重16至27千克、已插管并安装监测仪器的猪。
静脉注射油酸和吸入一氧化氮。
所有接受静脉注射油酸(0.11毫升/千克)治疗的猪均发生了伴有肺动脉高压的严重肺损伤,同时伴有氧合受损、肺内分流增加和血管外肺水增多(与基线相比,p < 0.05)。吸入一氧化氮后,尽管肺动脉高压呈剂量依赖性降低,但从动脉血氧分压(PaO2)和肺内分流情况来看,肺气体交换并未得到改善。在这个严重肺损伤模型中,一氧化氮代谢的稳定终产物血浆亚硝酸盐和硝酸盐浓度在一氧化氮暴露后并未升高。
在这个肺损伤模型中,吸入一氧化氮的作用仅限于缓解肺血管收缩,当严重肺损伤和肺泡-毛细血管屏障的炎症增厚导致气体扩散受损时,对改善肺气体交换的益处可能有限。在急性肺损伤的早期、不太严重的阶段使用吸入一氧化氮可能会有更好的效果。