Effects of short-term inhaled nitric oxide on interleukin-8 release after single-lung transplantation in pigs

Lung transplantation has evolved to become an effective treatment for a variety of end-stage lung diseases. However, severe reperfusion injury is still a major cause for postoperative morbidity and mortality. Although lung reperfusion injury is complex and has not been fully comprehended yet, neutrophil infiltration and cytokine activation have been postulated to play a main role. Recent studies showed that nitric oxide (NO) therapy has salutary effects on lung chronic and acute pathologies because it inhibits interleukin-8 (IL-8) release, but no data have been found on its effects during organ harvest. The aim of this study was to assess whether low doses of inhaled NO pre-treatment at the time of harvesting improves allograft function during early reperfusion in a porcine model.

Twenty-two Landrace pigs were randomly assigned to NO-treated and control groups. In NO-treated pigs, NO at 20 ppm was administered 30 min before harvest. During the early allograft reperfusion period IL-8 content, dynamic and static compliance and gas exchange (Pa/FiO2 and PaO2) were measured in both control and NO-treated lungs.

Pre-treatment with NO at the time of harvesting showed improvement of allograft function in terms of dynamic (92 +/- 8% in NO vs 72 +/- 7% in the control group, p < .05) and static (83 +/- 8% in NO vs 63 +/- 7% in the control group, p < 0.05) compliance and gas exchange (PaO2: 96 +/- 4% in NO vs 74 +/- 4.5% in the control group, p < 0.01; Pa/FiO2: 97 +/- 5% in NO vs 74 +/- 5% in the control group, p < 0.01) by diminishing IL-8 (66.5 +/- 4.7 pg/ml in NO versus 208 +/- 43 pg/ml in the control group, p < 0.05) release in pigs.

These results show for the first time that NO pre-treatment at the time of harvesting reduces allograft reperfusion injury in part due to its effects on IL-8 release.