Bland Richard D, Albertine Kurt H, Carlton David P, MacRitchie Amy J
Department of Pediatrics, Stanford University School of Medicine, CCSR Building, Room 1225, 269 Campus Drive, Stanford, CA 94305-5162, USA.
Am J Respir Crit Care Med. 2005 Oct 1;172(7):899-906. doi: 10.1164/rccm.200503-384OC. Epub 2005 Jun 23.
Inhaled nitric oxide (iNO) can reverse neonatal pulmonary hypertension and bronchoconstriction and reduce proliferation of cultured arterial and airway smooth muscle cells.
To see if continuous iNO from birth might reduce pulmonary vascular and respiratory tract resistance (PVR, RE) and attenuate growth of arterial and airway smooth muscle in preterm lambs with chronic lung disease.
Eight premature lambs received mechanical ventilation for 3 weeks, four with and four without iNO (5-15 ppm). Four term lambs, mechanically ventilated without iNO for 3 weeks, served as additional control animals.
PVR and RE were measured weekly. After 3 weeks, lung tissue was processed for quantitative image analysis of smooth muscle abundance around small arteries (SMart) and terminal bronchioles (SMtb). Radial alveolar counts were done to assess alveolar number. Endothelial NO synthase (eNOS) protein in arteries and airways was measured by immunoblot analysis.
At study's end, PVR was similar in iNO-treated and untreated preterm lambs; PVR was less in iNO-treated preterm lambs compared with term control animals. RE in iNO-treated lambs was less than 40% of RE measured in preterm control animals. SMart was similar in iNO-treated and both groups of control lambs; SMtb in lambs given iNO was significantly less (approximately 50%) than in preterm control animals. Radial alveolar counts of iNO-treated lambs were more than twice that of preterm control animals. eNOS was similar in arteries and airways of iNO-treated preterm lambs compared with control term lambs.
iNO preserves structure and function of airway smooth muscle and enhances alveolar development in preterm lambs with chronic lung disease.
吸入一氧化氮（iNO）可逆转新生儿肺动脉高压和支气管收缩，并减少培养的动脉和气道平滑肌细胞的增殖。
观察从出生开始持续吸入iNO是否可降低患有慢性肺病的早产羔羊的肺血管和呼吸道阻力（PVR、RE），并减轻动脉和气道平滑肌的生长。
八只早产羔羊接受了3周的机械通气，四只使用iNO（5 - 15 ppm），四只未使用。四只足月羔羊，未使用iNO进行3周机械通气，作为额外的对照动物。
每周测量PVR和RE。3周后，对肺组织进行处理，以对小动脉（SMart）和终末细支气管（SMtb）周围的平滑肌丰度进行定量图像分析。进行径向肺泡计数以评估肺泡数量。通过免疫印迹分析测量动脉和气道中的内皮型一氧化氮合酶（eNOS）蛋白。
在研究结束时，接受iNO治疗和未治疗的早产羔羊的PVR相似；与足月对照动物相比，接受iNO治疗的早产羔羊的PVR较低。接受iNO治疗的羔羊的RE不到早产对照动物测量值的40%。接受iNO治疗和两组对照羔羊的SMart相似；接受iNO治疗的羔羊的SMtb明显少于（约50%）早产对照动物。接受iNO治疗的羔羊的径向肺泡计数是早产对照动物的两倍多。与对照足月羔羊相比，接受iNO治疗的早产羔羊的动脉和气道中的eNOS相似。
iNO可保留患有慢性肺病的早产羔羊气道平滑肌的结构和功能，并促进肺泡发育。
