Inhaled nitric oxide effects on lung structure and function in chronically ventilated preterm lambs

被引:106
作者
Bland, RD
Albertine, KH
Carlton, DP
MacRitchie, AJ
机构
[1] Stanford Univ, Sch Med, Dept Pediat, Stanford, CA 94305 USA
[2] Univ Utah, Sch Med, Dept Pediat, Salt Lake City, UT 84112 USA
[3] Univ Wisconsin, Sch Med, Dept Pediat, Madison, WI USA
关键词
airway smooth muscle; bronchopulmonary dysplasia; enclothelial nitric oxide synthase; lung growth and development; neonatal chronic lung disease; pulmonary vascular and respiratory tract resistances;
D O I
10.1164/rccm.200503-384OC
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
Rationale: Inhaled nitric oxide (iNO) can reverse neonatal pulmonary hypertension and bronchoconstriction and reduce proliferation of cultured arterial and airway smooth muscle cells. Objectives: 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. Methods: Eight premature lambs received mechanical ventilation for 3 weeks, four with and four without iNO (5-15 ppm). Four term lambs, mechanically ventilated without NO for 3 weeks, served as additional control animals. Measurements: 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. Main Results: 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 R-E measured in preterm control animals. SMart was similar in NO-treated and both groups of control lambs; SMtb in lambs given iNO was significantly less (similar to 50%) than in preterm control animals. Radial alveolar counts of NO-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. Conclusions: iNO preserves structure and function of airway smooth muscle and enhances alveolar development in preterm lambs with chronic lung disease.
引用
收藏
页码:899 / 906
页数:8
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