EFFECTS OF INHALED NITRIC-OXIDE ON PULMONARY-EDEMA AND LUNG NEUTROPHIL ACCUMULATION IN SEVERE EXPERIMENTAL HYALINE-MEMBRANE DISEASE

To determine the effects of inhaled NO (iNO) on pulmonary edema and lu ng inflammation in experimental hyaline membrane disease (HMD), we mea sured the effects of iNO on pulmonary hemodynamics, gas exchange, pulm onary edema, and lung myeloperoxidase (MPO) activity in extremely prem ature lambs (115 d of gestation, 0.78 term). In protocol I, we measure d the effects of iNO (20 ppm) on lung vascular endothelial permeabilit y to I-125-labeled albumin (indexed to blood volume using Cr-57-tagged red blood cells) during 1 h (n = 10) and 3 h (n = 14) of conventional mechanical ventilation with Fio(2) = 1.00. In comparison with control s, iNO improved pulmonary hemodynamics and gas exchange, but did not a lter lung weight-to-dry weight ratio or vascular permeability to album in after 1 or 3 h of mechanical ventilation. To determine whether low dose iNO (5 ppm) would decrease lung neutrophil accumulation in severe HMD, we measured lung MPO activity after 4 h of mechanical ventilatio n with or without iNO (protocol 2). Low dose iNO improved gas exchange during 4 h of mechanical ventilation (Pao, at 4 h: 119 +/- 35 mm Hg i NO versus 41 +/- 7 mmHg control, p < 0.05), and reduced MPO activity b y 79% (p < 0.05). We conclude that low dose iNO increases pulmonary bl ood flow, without worsening pulmonary edema, and decreases lung neutro phil accumulation in severe experimental HMD. We speculate that in add ition to its hemodynamic effects, low dose iNO decreases early neutrop hil recruitment and may attenuate lung injury in severe HMD.