Inhaled Nitric Oxide for High-Altitude Pulmonary Edema

Abstract

Background. Pulmonary hypertension is a hallmark of high-altitude pulmonary edema and may contribute to its pathogenesis. When administered by inhalation, nitric oxide, an endothelium-derived relaxing factor, attenuates the pulmonary vasoconstriction produced by short-term hypoxia. Methods. We studied the effects of inhaled nitric oxide on pulmonary-artery pressure and arterial oxygenation in 18 mountaineers prone to high-altitude pulmonary edema and 18 mountaineers resistant to this condition in a high-altitude laboratory (altitude, 4559 m). We also obtained lung-perfusion scans before and during nitric oxide inhalation to gain further insight into the mechanism of action of nitric oxide. Results. In the high-altitude laboratory, subjects prone to high-altitude pulmonary edema had more pronounced pulmonary hypertension and hypoxemia than subjects resistant to high-altitude pulmonary edema. Arterial oxygen saturation was inversely related to the severity of pulmonary hypertension (r = -0.50, P = 0.002). In subjects prone to high- altitude pulmonary edema, the inhalation of nitricoxide (40 ppm for 15 minutes) produced a decrease in mean (±SD) systolic pulmonary-artery pressure that was three times larger than the decrease in subjects resistent to such edema (25.9 ± 8.9 vs. 8.7 ± 4.8 mm Hg, P < 0.001). Inhaled nitric oxide improved arterial oxygenation in the 10 subjects who had radiographic evidence of pulmonary edema (arterial oxygen saturation increased from 67 ± 10 to 73 ± 12 percent, P = 0.047), whereas it worsened oxygenation in subjects resistant to high-altitude pulmonary edema. The nitric oxide- induced improvement in arterial oxygenation in subjects with high-altitude pulmonary edema was accompanied by a shift in blood flow in the lung away from edematous segments and toward nonedematous segments. Conclusions. The inhalation of nitric oxide improves arterial oxygenation in high-altitude pulmonary edema, and this beneficial effect may be related to its favorable action on the distribution of blood flow in the lungs. A defect in nitric oxide synthesis may contribute to high-altitude pulmonary edema.