Disparate effects of nitric oxide on lung ischemia-reperfusion injury.
BACKGROUND
Inhaled nitric oxide (.NO) has been found to be a potent pulmonary vasodilator. We assessed whether .NO, through this function or others, could alleviate lung reperfusion injury.


METHODS
Rats underwent thoracotomy, with clamps used to create left lung ischemia. After 90 minutes of ischemia, clamps were released, permitting reperfusion for either 30 minutes or 4 hours. Additional animals received inhaled .NO via the ventilator to determine its effects on reperfusion injury.


RESULTS
Lung injury, measured by increased vascular permeability using iodine-125-labeled bovine serum albumin leakage, was significantly increased in ischemic-reperfused animals compared with time-matched shams not undergoing ischemia. Inhaled .NO delivered at the start of reperfusion worsened injury at 30 minutes but was protective at 4 hours. The increased injury could be avoided either by delaying .NO for 10 minutes or by treating the animals with superoxide dismutase before reperfusion. .NO reversed postischemic pulmonary hypoperfusion at 4 hours, as measured by labeled microspheres. Lung neutrophil content was significantly reduced at 4 hours in .NO-treated animals.


CONCLUSIONS
.NO is toxic early in reperfusion, due to its interaction with superoxide, but is protective at 4 hours of reperfusion, due to reversal of postischemic lung hypoperfusion and reduction of lung neutrophil sequestration.
Section of Thoracic Surgery, University of Michigan Medical Center, Ann Arbor, USA.
M J
MJ
Eppinger
P A
PA
Ward
M L
ML
Jones
S F
SF
Bolling
G M
GM
Deeb
D000280:Administration, Inhalation; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D008168:Lung / Q000098:blood supply*; D008297:Male; D009504:Neutrophils / Q000473:pathology; D009569:Nitric Oxide / Q000494:pharmacology / Q000627:therapeutic use*; D011292:Premedication; D011652:Pulmonary Circulation / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D015427:Reperfusion Injury / Q000175:diagnosis / Q000188:drug therapy*; D013482:Superoxide Dismutase / Q000627:therapeutic use; D013997:Time Factors
D009569:Nitric Oxide; D013482:Superoxide Dismutase