Young Karen C, Ladino John, Navarrete Cristina, Dabrowska Katarzyna, Hehre Dorothy, Bancalari Eduardo, Suguihara Cleide
Division of Neonatology, Department of Pediatrics, University of Miami School of Medicine, Miami, FL 33101, USA.
Biol Neonate. 2004;85(3):195-202. doi: 10.1159/000075815. Epub 2003 Dec 24.
NONOates, novel NO donors, are complexes of NO with nucleophiles which spontaneously and nonenzymatically release NO in aqueous solution. This study sought to determine the cardiopulmonary effects of the nebulized NONOate dipropylenetriamine (DPTA)/NO in newborn piglets with acute hypoxia-induced pulmonary hypertension. Twenty sedated and mechanically ventilated piglets (4-10 days old) exposed to hypoxia (Fi(O2) = 0.14) were randomly assigned to receive nebulized saline as placebo (PL) or DPTA/NO (75 mg) after 30 min of hypoxia. Pulmonary artery (P(pa)) and wedge pressures, systemic (P(sa)) and right atrial pressures, cardiac output (CO) and arterial blood gas were measured at baseline and every 15 min for 2 h. Methemoglobin levels were measured at baseline and 1 h after drug nebulization. Data (means +/- SD) were analyzed by repeated-measures analysis of variance. Acute hypoxia resulted in an increase in P(pa) and pulmonary vascular resistance (PVR), which was significantly attenuated by DPTA/NO nebulization as compared to the PL group (p < 0.0001). Changes in P(sa), CO, systemic vascular resistance (SVR), arterial blood gas and methemoglobin levels were not different between groups. In contrast to the increase in PVR/SVR observed during hypoxia in the PL group, there was a significant decrease in this ratio after NONOate administration (p < 0.0001). These data show that acute hypoxic pulmonary hypertension in newborn piglets is markedly attenuated by NONOate nebulization. This response is predominantly in the pulmonary vasculature as the PVR/SVR was significantly lower in the treated group. We speculate that NONOates may have clinical application in the treatment of persistent pulmonary hypertension of the newborn.
NONOates是新型一氧化氮供体，是一氧化氮与亲核试剂的复合物，可在水溶液中自发且非酶促地释放一氧化氮。本研究旨在确定雾化吸入NONOate二亚丙基三胺（DPTA）/一氧化氮对急性低氧诱导的肺动脉高压新生仔猪的心肺影响。20只接受镇静并机械通气的仔猪（4 - 10日龄）暴露于低氧环境（吸入氧分数（Fi(O2)）= 0.14），在低氧30分钟后随机分为两组，分别接受雾化生理盐水作为安慰剂（PL）或DPTA/一氧化氮（75毫克）。在基线时以及之后2小时内每15分钟测量肺动脉（P(pa)）和楔压、体循环（P(sa)）和右心房压力、心输出量（CO）以及动脉血气。在基线时和雾化药物1小时后测量高铁血红蛋白水平。数据（均值±标准差）采用重复测量方差分析进行分析。急性低氧导致P(pa)和肺血管阻力（PVR）增加，与PL组相比，DPTA/一氧化氮雾化显著减轻了这种增加（p < 0.0001）。两组之间P(sa)、CO、体循环血管阻力（SVR）、动脉血气和高铁血红蛋白水平的变化无差异。与PL组在低氧期间观察到的PVR/SVR增加相反，NONOate给药后该比值显著降低（p < 0.0001）。这些数据表明，雾化吸入NONOate可显著减轻新生仔猪的急性低氧性肺动脉高压。这种反应主要发生在肺血管系统，因为治疗组的PVR/SVR显著降低。我们推测NONOates可能在新生儿持续性肺动脉高压的治疗中具有临床应用价值。
