Disparate effects of nitric oxide on lung ischemia-reperfusion injury

Ann Thorac Surg. 1995 Nov;60(5):1169-75; discussion 1176. doi: 10.1016/0003-4975(95)00697-J.


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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Inhalation
  • Animals
  • Capillary Permeability / drug effects
  • Drug Evaluation, Preclinical
  • Lung / blood supply*
  • Male
  • Neutrophils / pathology
  • Nitric Oxide / pharmacology
  • Nitric Oxide / therapeutic use*
  • Premedication
  • Pulmonary Circulation / drug effects
  • Rats
  • Rats, Inbred Strains
  • Reperfusion Injury / diagnosis
  • Reperfusion Injury / drug therapy*
  • Superoxide Dismutase / therapeutic use
  • Time Factors


  • Nitric Oxide
  • Superoxide Dismutase