吸入一氧化氮治疗胎粪吸入综合征的实验研究

Experimental study on treatment of meconium aspiration syndrome with inhaled nitric oxide

目的 建立新生猪胎粪吸入综合征 (MAS)动物模型 ;评价吸入一氧化氮 (NO)的疗效及对机体的其他影响。方法 日龄 7d以内健康新生猪在机械通气条件下 ,吸入 2 0 %胎粪盐水 (MNS)4～ 6ml kg制成重症MAS模型。观察NO治疗前后血气、循环指标、高铁血红蛋白 (MHb)、肺组织匀浆丙二醛 (MDA)含量的变化及肺组织病理改变。结果 新生猪吸入胎粪后出现重症MAS的临床表现 :低氧血症 [动脉血氧分压 (PaO2 ) <6 0mmHg],动脉与肺泡氧分压之比 (a APO2 ) <0 .2 ]、酸中毒 (pH值<7.3)、肺动脉压升高 (≥ 2 5mmHg)。吸入 2 0× 10 - 6 或 40× 10 - 6 NO均可迅速纠正低氧血症、降低肺动脉压 [PaO2 分别由 (5 0± 7)、(4 6± 6 )mmHg上升至 (115± 34)、(85± 2 3)mmHg (P <0 .0 1) ;PAP分别由 (32± 6 )、(2 4± 3)mmHg下降至 (2 1± 3)、(17± 4)mmHg]。吸入不同浓度的NO两组间疗效差异无显著性 ,体循环稳定。短期 (2h)吸入NO治疗不会引起高铁血红蛋白血症、肺组织氧自由基升高等毒副作用 ;不能抑制肺组织炎症损伤。结论 短期 (≤ 2h)、低浓度 (≤ 40× 10 - 6 )吸入NO治疗MAS迅速、安全、有效。治疗重症MAS宜采用包括吸入NO在内的综合治疗措施。

Objective The meconium aspiration syndrome (MAS) is a frequent cause of respiratory disease among neonates. MAS occurs in 2%～4% of all live births. The mortality rate for severe MAS remains greater than 50%. The aim of this study was to reproduce the animal model of piglet MAS and to evaluate the effect of inhaled nitric oxide (INO)therapy. Methods Healthy 3 to 7 day old newborn piglets were intubated and received an intratrachael bolus of 4 to 6 ml/kg of 20% meconium in normal saline, and severe MAS was caused,as demonstrated by hypoxemia (PaO 2<60 mm Hg, a/APO 2<0.2), acidosis (pH<7.3), pulmonary hypertension (PAP≥25 mm Hg). Then the arterial blood gas and hemodynamic parameters were recorded,the changes of methomoglobin(MHb) in blood,the quantity of malondialdehyde(MDA) in the lung and the pulmonary pathology were observed. Results Conventional therapy couldn't effectively treat hypoxemia and pulmonary hypertension: before and after the intervention, PaO 2, PAP were (46±14) mm Hg, (24±5) mm Hg,(59±13) mm Hg, and (20±9) mm Hg ( P >0.05), respectively. Hypoxemia and pulmonary hypertension were quickly corrected by INO, PaO 2 increased from (50±7) mm Hg to (115±34) mm Hg, and PAP decreased from (32±6) mm Hg to (21±3) mm Hg after receiving 20×10 -6 NO ( P <0.01). After receiving 40×10 -6 NO, PaO 2 increased from (46±6) mm Hg to (85±23) mm Hg and PAP decreased from (24±3) mm Hg to (17±4) mm Hg ( P < 0.01). Serious side effects such as methemoglobinemia were not found. The pulmonary inflammatory injury couldn't be inhibited by INO therapy. Conclusion INO therapy seemed to be effective and safe. It is important that compound strategies, including INO, should be applied when rescuing serious MAS.