Acute hypoxia and reoxygenation impairs exhaled nitric oxide release and pulmonary mechanics.
OBJECTIVE
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 micromol/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 micromol/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 H(2)O at baseline, 5.0 +/- 0.7 mL/cm H(2)O at end hypoxia, and 5.4 +/- 0.7 mL/cm H(2)O at end recovery), and increased inspiratory airway resistance (41 +/- 4 cm H(2)O. L(-1). s(-1) at baseline, 56 +/- 4.9 cm H(2)O. L(-1). s(-1) at end hypoxia, and 50 +/- 5 cm H(2)O. 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.
Pearl
J M
JM
Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA. pearj0@chmcc.org
Nelson
D P
DP
Wellmann
S A
SA
Raake
J L
JL
Wagner
C J
CJ
McNamara
J L
JL
Duffy
J Y
JY
D000208:Acute Disease; D000403:Airway Resistance; D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers / Q000032:analysis; D001944:Breath Tests; D002302:Cardiac Output; D002315:Cardiopulmonary Bypass; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology / Q000628:therapy; D008054:Lipid Peroxides / Q000378:metabolism; D008168:Lung / Q000098:blood supply / Q000378:metabolism* / Q000503:physiopathology; D008170:Lung Compliance; D009569:Nitric Oxide / Q000032:analysis / Q000378:metabolism*; D009573:Nitrites / Q000097:blood; D009195:Peroxidase / Q000378:metabolism; D011659:Pulmonary Gas Exchange; D020127:Recovery of Function; D013552:Swine; D014655:Vascular Resistance
D015415:Biomarkers; D008054:Lipid Peroxides; D009573:Nitrites; D009569:Nitric Oxide; D009195:Peroxidase