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

• Published in: American journal of respiratory and critical care medicine Vol. 172; no. 7; pp. 899 - 906
• Main Authors: Bland, Richard D, Albertine, Kurt H, Carlton, David P, MacRitchie, Amy J
• Format: Journal Article
• Language: English
• Published: New York, NY Am Thoracic Soc 01-10-2005; American Lung Association; American Thoracic Society
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Animals, Newborn; Biological and medical sciences; Blood vessels; Blood. Blood coagulation. Reticuloendothelial system; Cells, Cultured; Chronic Disease; Disease Models, Animal; E. Pediatrics and Lung Development; Emergency and intensive respiratory care; Hypotheses; Image Processing, Computer-Assisted; Intensive care medicine; Lung diseases; Lung Diseases - physiopathology; Lungs; Medical sciences; Muscle, Smooth - drug effects; Newborn babies; Nitric oxide; Nitric Oxide - pharmacology; Pharmacology. Drug treatments; Proteins; Pulmonary Alveoli - drug effects; Pulmonary Alveoli - physiology; Pulmonary arteries; Pulmonary hypertension; Respiration - drug effects; Respiration, Artificial; Respiratory failure; Sheep; Smooth muscle; Veins & arteries; Ventilators; Premature; Intensive care; Smooth muscle; pulmonary vascular and respiratory tract resistances; Respiratory system; Lamb; Respiratory tract; Lung function; Vascular resistance; Bronchus disease; endothelial nitric oxide synthase; lung growth and development; Ungulata; Resuscitation; Human; Lung disease; Respiratory disease; Enzyme; Chronic disease; airway smooth muscle; Nitric-oxide synthase; Inhalation; Newborn diseases; Vertebrata; Mammalia; Newborn; Prematurity; Nitric oxide; neonatal chronic lung disease; Sheep; Bronchopulmonary dysplasia; Artiodactyla; Oxidoreductases
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/rccm.200503-384OC

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.