Acute hypoxia and reoxygenation impairs exhaled nitric oxide release and pulmonary mechanics

AbstractObjective: Changes in exhaled nitric oxide levels often accompany conditions associated with elevated pulmonary vascular resistance and altered lung mechanics. However, it is unclear whether changes in exhaled nitric oxide reflect altered vascular or bronchial nitric oxide production. This study determined the effects of acute hypoxia and reoxygenation on pulmonary mechanics, plasma nitrite levels, and exhaled nitric oxide production. Methods: Ten piglets underwent 90 minutes of hypoxia (fraction of inspired oxygen = 12%), 1 hour of reoxygenation on cardiopulmonary bypass, and 2 hours of recovery. Five additional animals underwent bypass without hypoxia. Exhaled nitric oxide, plasma nitrite levels, and pulmonary mechanics were measured. Results: Exhaled nitric oxide decreased to 36% of baseline by end hypoxia (34 ± 14 vs 12 ± 9 ppb, P = .005) and declined further to 20% of baseline at end recovery (7 ± 6 ppb). Aortic nitrite levels decreased from baseline during hypoxia (from 102 ± 13 to 49 ± 7 μmol/L, P = .05) but returned to baseline during recovery. Pulmonary arterial nitrite also decreased during hypoxia (from 31.4 ± 7.8 to 22.9 ± 9.5 μmol/L, P = .04) and returned to baseline at end recovery. Decreased production of exhaled nitric oxide was associated with impaired gas exchange (alveolar-arterial gradient = 32 mm Hg at baseline and 84 mm Hg at end recovery), decreased pulmonary compliance (6.6 ± 0.9 mL/cm H2O at baseline, 5.0 ± 0.7 mL/cm H2O at end hypoxia, and 5.4 ± 0.7 mL/cm H2O at end recovery), and increased inspiratory airway resistance (41 ± 4 cm H2O · L–1 · s–1 at baseline, 56 ± 4.9 cm H2O · L–1 · s–1 at end hypoxia, and 50 ± 5 cm H2O · L–1 · s–1 at end recovery). Conclusions: A decrease in exhaled nitric oxide persisted after hypoxia, and plasma nitrite levels returned to baseline on reoxygenation, indicating that alterations in exhaled nitric oxide during hypoxia-reoxygenation might be unrelated to plasma nitrite levels. Furthermore, decreased exhaled nitric oxide corresponded with altered pulmonary mechanics and gas exchange. Reduced exhaled nitric oxide after hypoxia-reoxygenation might reflect bronchial epithelial dysfunction associated with acute lung injury. (J Thorac Cardiovasc Surg 2000;119:931-8