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Published ahead of print on June 23, 2005, doi:10.1164/rccm.200503-384OC
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American Journal of Respiratory and Critical Care Medicine Vol 172. pp. 899-906, (2005)
© 2005 American Thoracic Society
doi: 10.1164/rccm.200503-384OC

Original Article

Inhaled Nitric Oxide Effects on Lung Structure and Function in Chronically Ventilated Preterm Lambs

Richard D. Bland, Kurt H. Albertine, David P. Carlton and Amy J. MacRitchie

Department of Pediatrics, Stanford University School of Medicine, Stanford University, Stanford, California; Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, Utah; and Department of Pediatrics, University of Wisconsin School of Medicine, Madison, Wisconsin

Correspondence and requests for reprints should be addressed to Richard D. Bland, M.D., Professor of Pediatrics, Stanford University School of Medicine, CCSR Building, Room 1225, 269 Campus Drive, Stanford, CA 94305-5162. E-mail: rbland{at}stanford.edu

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 iNO 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 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 (~ 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.

Conclusions: iNO preserves structure and function of airway smooth muscle and enhances alveolar development in preterm lambs with chronic lung disease.

Key Words: airway smooth muscle • bronchopulmonary dysplasia • endothelial nitric oxide synthase • lung growth and development • neonatal chronic lung disease • pulmonary vascular and respiratory tract resistances




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