Ventilation-perfusion mismatch after lung ischemia-reperfusion. Protective effect of nitric oxide

Am J Respir Crit Care Med. 1999 Oct;160(4):1179-87. doi: 10.1164/ajrccm.160.4.9808034.


Lung ischemia-reperfusion provokes pulmonary hypertension and increased microvascular permeability with subsequent edema formation and hypoxemia. We exposed buffer-perfused rabbit lungs to 120 and 180 min of warm ischemia. After reperfusion, gas exchange disturbances were analyzed by the multiple inert gas elimination technique (MIGET). Additionally, ischemic lungs were treated with different doses of inhaled nitric oxide (NO) throughout reperfusion. Reperfusion provoked a transient pulmonary artery pressure elevation, followed by progressive pulmonary edema formation. After 120 min of ischemia, severe ventilation-perfusion (V A/Q) mismatch developed within 15 min of reperfusion, with the appearance of low V A/Q areas and marked broadening of both perfusion and ventilation distribution in the midrange V A/Q regions. In parallel, shunt flow increased from less than 2% to approximately 17%. Inhalation of NO suppressed the pressor response, edema formation, as well as V A/Q mismatch and shunt flow. Concentrations of 10 and 50 ppm NO were equipotent, surpassing the efficacy of 1 or 250 ppm NO. Inhalation of NO, however, did not protect from the overwhelming gas exchange and fluid balance disturbances provoked by 180 min ischemia. In conclusion, severe abnormalities in gas exchange occurred rapidly upon reperfusion of ischemic lungs. Prophylactic NO inhalation may be considered for maintenance of gas exchange in settings of ischemia-reperfusion including lung transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Animals
  • Blood Pressure
  • Capillary Permeability
  • Hypertension, Pulmonary / etiology
  • Hypertension, Pulmonary / physiopathology*
  • In Vitro Techniques
  • Ischemia / physiopathology
  • Lung / blood supply
  • Nitric Oxide / administration & dosage
  • Nitric Oxide / pharmacology*
  • Pulmonary Circulation
  • Pulmonary Edema / etiology
  • Pulmonary Edema / physiopathology*
  • Pulmonary Gas Exchange
  • Rabbits
  • Reperfusion Injury / physiopathology*
  • Vasodilator Agents / administration & dosage
  • Vasodilator Agents / pharmacology*
  • Ventilation-Perfusion Ratio*


  • Vasodilator Agents
  • Nitric Oxide