Valiño Fernando, Casals Cristina, Guerrero Rosa, Alvarez Lourdes, Santos Martín, Sáenz Alejandra, Varela Andrés, Claro Miguel A, Tendillo Francisco, Castillo-Olivares José L
Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, Madrid, Spain.
Transplantation. 2004 Mar 27;77(6):812-8. doi: 10.1097/01.tp.0000116421.57232.81.
Inhalation of nitric oxide (NO) has been proposed as a therapy to improve lung transplantation outcome. We investigated the effect that inhaled NO has on the surfactant system in the context of ischemia-reperfusion injury.
Single left-lung transplantation was performed in weight-matched pairs of Landrace pigs. A double-lung block from the donor animal was flushed with University of Wisconsin solution at 4 degrees C followed by immersion in cold University of Wisconsin solution for 22 hr. The left donor lung was transplanted into the recipient. Recipients were divided into two groups: (1) treated with inhaled NO (40 ppm) (n=6) immediately after initiating lung reperfusion and (2) without treatment (n=6). Lung function was measured during 2 hr of reperfusion. Surfactant components in small and large aggregates, isolated from cell-free bronchoalveolar lavages, and surfactant function were measured.
NO inhalation significantly decreased arterial oxygenation. With respect to the surfactant system, NO inhalation worsened the surfactant adsorption rate to an air-liquid interface and affected levels of hydrophobic surfactant proteins (SPs), SP-B and SP-C, and phospholipids, which decreased in large surfactant aggregates but not in small surfactant aggregates. SP-A was reduced in large surfactant aggregates of transplanted lungs from both untreated and NO-treated groups.
A decreased level of SP-A, SP-B, and SP-C in large surfactant aggregates of transplanted lungs treated with NO is a marker of lung injury. We conclude that treatment with inhaled NO after lung transplantation is deleterious for the surfactant system and causes a parallel worsening of arterial oxygenation.
吸入一氧化氮（NO）已被提议作为一种改善肺移植结果的治疗方法。我们研究了在缺血再灌注损伤背景下吸入NO对表面活性剂系统的影响。
在体重匹配的长白猪对中进行单左肺移植。将供体动物的双肺块用4℃的威斯康星大学溶液冲洗，然后浸入冷的威斯康星大学溶液中22小时。将左供体肺移植到受体中。受体分为两组：（1）在肺再灌注开始后立即用吸入NO（40 ppm）治疗（n = 6）；（2）不治疗（n = 6）。在再灌注2小时期间测量肺功能。测量从无细胞支气管肺泡灌洗中分离出的小和大聚集体中的表面活性剂成分以及表面活性剂功能。
吸入NO显著降低动脉氧合。关于表面活性剂系统，吸入NO使表面活性剂在气液界面的吸附率恶化，并影响疏水表面活性剂蛋白（SPs）、SP-B和SP-C以及磷脂的水平，这些在大表面活性剂聚集体中降低，但在小表面活性剂聚集体中未降低。在未治疗组和NO治疗组的移植肺的大表面活性剂聚集体中，SP-A均降低。
用NO治疗的移植肺的大表面活性剂聚集体中SP-A、SP-B和SP-C水平降低是肺损伤的标志物。我们得出结论，肺移植后吸入NO治疗对表面活性剂系统有害，并导致动脉氧合同时恶化。
