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

Objective: Changes in exhaled nitric oxide levels often accompany condition s associated with elevated pulmonary vascular resistance and altered lung m echanics. However, it is unclear whether changes in exhaled nitric oxide re flect altered vascular or bronchial nitric oxide production. This study det ermined the effects of acute hypoxia and reoxygenation on pulmonary mechani cs, 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 hou rs of recovery. Five additional animals underwent bypass without hypoxia. E xhaled nitric oxide, plasma nitrite levels, and pulmonary mechanics were me asured. 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 baselin e at end recovery (7 +/- 6 ppb). Aortic nitrite levels decreased from basel ine during hypoxia (from 102 +/- 13 to 49 +/- 7 mu mol/L, P = .05) but retu rned to base line during recovery. Pulmonary arterial nitrite also decrease d during hypoxia (from 31.4 +/- 7.8 to 22.9 +/- 9.5 mu mol/L, P = .04) and returned to baseline at end recovery. Decreased production of exhaled nitri c oxide was associated with impaired gas exchange (alveolar-arterial gradie nt = 32 mm HE at baseline and 84 mm Hg at end recovery), decreased pulmonar y compliance (6.6 +/- 0.9 mL/cm H2O at baseline, 5.0 +/- 0.7 mL/cm H2O at e nd hypoxia, and 5.4 +/- 0.7 mL/cm H2O at end recovery), and increased inspi ratory 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 reco very). Conclusions: A decrease in exhaled nitric oxide persisted after hypoxia, an d plasma nitrite levels returned to baseline on reoxygenation, indicating t hat alterations in exhaled nitric oxide during hypoxia-reoxygenation might be unrelated to plasma nitrite levels. Furthermore, decreased exhaled nitri c oxide corresponded with altered pulmonary mechanics and gas exchange. Red uced exhaled nitric oxide after hypoxia-reoxygenation might reflect bronchi al epithelial dysfunction associated with acute lung injury.