Kinsella John P, Parker Thomas A, Davis Jonathan M, Abman Steven H
Department of Pediatrics, Pediatric Heart-Lung Center, Section of Neonatology, University of Colorado School of Medicine, Denver, Colorado, USA.
Am J Respir Crit Care Med. 2005 Sep 15;172(6):745-9. doi: 10.1164/rccm.200501-146OC. Epub 2005 Jun 9.
Oxidant stress may increase the severity of respiratory distress syndrome (RDS) after premature birth by altering vasoreactivity and increasing lung edema, but the acute effects of superoxide dismutase (SOD) treatment on gas exchange, lung compliance (CL), and pulmonary vascular resistance in premature animals with RDS are unknown.
We studied the effects of intratracheal recombinant human SOD treatment (rhSOD) on gas exchange, CL, and pulmonary hemodynamics in 46 premature lambs with RDS.
After C-section delivery, lambs were randomly assigned to treatment with SOD (2.5-10 mg/kg) with or without inhaled nitric oxide (iNO, 5 ppm), and mechanically ventilated for 4 hours. At the end of the study, pressure-volume curves and wet-dry lung weights were measured to assess CL and edema, respectively.
Despite an initial rise in Pa(O(2)), Pa(O(2)) in control animals progressively declined over the 4-hour treatment period (Pa(O(2)) = 25.0 +/- 7.5 mm Hg at 4 hours). In comparison with control animals, early treatment with SOD at 5 and 10 mg/kg improved Pa(O(2)) at 4 hours (167 +/- 44 and 269 +/- 33 mm Hg, respectively; p < 0.05 vs. control), but did not decrease lung edema or improve CL. In contrast, late treatment with SOD did not improve Pa(O(2)). Treatment with iNO increased Pa(O(2)) (196 +/- 22 vs. 25 +/- 8 mm Hg, control animals; p < 0.01), but the response to iNO was not augmented by combined therapy (SOD + iNO). After 4 hours of ventilation with FI(O(2)) = 1.00, rhSOD treatment lowered pulmonary vascular resistance compared with control animals.
Early intratracheal rhSOD treatment improves oxygenation in premature lambs with RDS and prevents the development of pulmonary hypertension.
氧化应激可能通过改变血管反应性和增加肺水肿来加重早产后脑呼吸窘迫综合征（RDS）的严重程度，但超氧化物歧化酶（SOD）治疗对患有RDS的早产动物气体交换、肺顺应性（CL）和肺血管阻力的急性影响尚不清楚。
我们研究了气管内给予重组人SOD治疗（rhSOD）对46只患有RDS的早产羔羊气体交换、CL和肺血流动力学的影响。
剖宫产分娩后，羔羊被随机分配接受SOD（2.5 - 10mg/kg）治疗，联合或不联合吸入一氧化氮（iNO，5ppm），并机械通气4小时。在研究结束时，测量压力 - 容积曲线和肺湿重与干重以分别评估CL和水肿。
尽管对照组动物的Pa(O₂)最初有所上升，但在4小时的治疗期间，对照组动物的Pa(O₂)逐渐下降（4小时时Pa(O₂) = 25.0±7.5mmHg）。与对照组动物相比，5mg/kg和10mg/kg的SOD早期治疗在4小时时改善了Pa(O₂)（分别为167±44和269±33mmHg；与对照组相比，p < 0.05），但并未减轻肺水肿或改善CL。相比之下，SOD晚期治疗并未改善Pa(O₂)。iNO治疗增加了Pa(O₂)（对照组动物为196±22 vs. 25±8mmHg；p < 0.01），但联合治疗（SOD + iNO）并未增强对iNO的反应。在Fi(O₂) = 1.00通气4小时后，与对照组动物相比，rhSOD治疗降低了肺血管阻力。
早期气管内给予rhSOD治疗可改善患有RDS的早产羔羊的氧合，并预防肺动脉高压的发生。
