Nitric oxide inhalation inhibits pulmonary apoptosis but not inflammatory injury in porcine meconium aspiration.
To investigate the possible protective effects of nitric oxide (NO) inhalation in newborns with meconium aspiration, 18 10-12-d-old piglets were studied for 6h after an intratracheal bolus (3 ml/kg) of a 65-mg/ml mixture of human meconium. Twelve of the piglets were treated with continuous NO inhalation at a dose of 1 ppm (n = 6) or 10 ppm (n = 6), started 30 min before the insult. Pulmonary haemodynamics and systemic oxygenation were followed, and lung tissue samples were studied for signs of inflammation, evidence of ultrastructural injury and apoptotic cell changes. Inhalation of 10 ppm NO, in contrast to 1 ppm NO, significantly delayed the meconium-induced pulmonary pressure rise and the increase in intrapulmonary shunt fraction, and maintained better oxygenation in the piglets. Histologically and biochemically, treatment with 1 or 10 ppm NO inhalation did not protect the lungs against meconium-induced inflammatory injury. Further, ultrastructural lung tissue analysis revealed a significant amount of alveolar exudate and oedematous alveolar epithelium and endothelium after meconium instillation, also in the lungs treated with NO inhalation. However, the increase in apoptotic epithelial cell deaths, previously shown to be stimulated by intratracheal meconium, was significantly impeded after inhalation of 10 ppm. These results thus show that early continuous NO inhalation controls the rise in pulmonary artery pressure and improves the efficiency of arterial oxygenation, and further prevents the increase in epithelial apoptosis, but does not protect against early inflammatory damage caused by meconium aspiration.
Holopainen
R
R
Cardiorespiratory Research Unit, University of Turku, Finland.
Aho
H
H
Laine
J
J
Halkola
L
L
Kääpä
P
P
D000280:Administration, Inhalation; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects*; D001993:Bronchodilator Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D004721:Endoplasmic Reticulum / Q000648:ultrastructure; D006801:Humans; D007231:Infant, Newborn; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008471:Meconium Aspiration Syndrome / Q000150:complications / Q000188:drug therapy*; D008854:Microscopy, Electron; D008928:Mitochondria / Q000648:ultrastructure; D009569:Nitric Oxide / Q000008:administration & dosage*; D011014:Pneumonia / Q000188:drug therapy / Q000209:etiology / Q000473:pathology*; D011650:Pulmonary Alveoli / Q000648:ultrastructure; D012016:Reference Values; D013552:Swine
D001993:Bronchodilator Agents; D009569:Nitric Oxide