Experimental and clinical studies on inhalaed nitric oxide therapy in pediatric surgery

一氧化氮(NO)已被成功地用于治疗肺动脉高压。本研究旨在探讨NO吸入治疗对急性肺损伤合并肺动脉高压的影响。[1：实验研究]动物接受四种治疗方法之一：静脉注射内毒素、静脉注射胰酶、气管内注入盐酸和100%氧气。(1)吸入NO(5~20ppm)可减轻内毒素或胰酶所致的肺动脉高压。这些剂量的NO对全身血压没有影响。(2)吸入NO可减轻各模型大鼠肺组织形态改变。(3)吸入NO组支气管肺泡灌洗液中中性粒细胞数量低于未吸入组，提示NO抑制细胞聚集和黏附。(4)所有兔的高铁血红蛋白水平均不超过1.5%。[2：临床研究]未制备新生儿和儿童吸入系统。9例新生儿持续性肺动脉高压(PPHN)患者不吸入(20ppm持续4小时，6ppm持续20小时)。9例新生儿中有8例氧合指数未改善20%，有效率为89%。这些实验和临床研究结果表明，吸入NO治疗急性肺损伤和肺动脉高压是有效的。

Nitric oxide (NO) has been successfully used for treatment of pulmonary hypertension. The aim of our studies was to investigate the effect of NO inhalation therapy on acute lung injury associated with pulmonary hypertension.[1 : Experimental Study]The animals received one of four treatment : intravenous endotoxin, intravenous trypsin, intratracheal HCl, and ventilation with 100% oxygen. (1) Pulmonary hypertension induced by endotoxin or trypsin was attenuated by NO (5-20 ppm) inhalation. NO at these doses had no effect on systemic blood pressure. (2) Inhaled NO attenuated morphological changes in any model. (3) The number of neutrophils in bronchoalveolar lavage fluid was lower in NO inhalation group than in NO non-treated group suggesting that NO inhibited aggregation and adhesion of the cells. (4) Methemoglobin levels did not exceed 1.5% in any rabbit.[2 : Clinical Study]NO inhalation system for neonates and children was prepared. Nine patients with persistent pulmonary hypertension of neonates (PPHN) received NO inhalation (20 ppm for 4 hr and 6 ppm for 20 hr) . In 8 of 9 neonates, NO improved oxygenation index by 20% : the efficacy was 89%. In some cases, NO inhalation facilitated weaning from ECMO.In conclusion, these results of the experimental and clinical studies suggest that NO inhalation therapy is useful for acute lung injury and pulmonary hypertension.