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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Gómez
Carmen B
CB
Institute of Cardiology and Cardiovascular Surgery of the Favaloro Foundation, Buenos Aires, Argentina. cgomez@ffavaloro.org
del Valle
Héctor F
HF
Bertolotti
Alejandro
A
Negroni
Jorge A
JA
Cuniberti
Luis
L
Martínez
Verónica
V
Ossés
Juan
J
Laguens
Rubén P
RP
Favaloro
Roberto R
RR
D000280:Administration, Inhalation; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D045462:Endothelium-Dependent Relaxing Factors / Q000008:administration & dosage*; D016209:Interleukin-8 / Q000378:metabolism*; D008168:Lung / Q000378:metabolism / Q000473:pathology; D016040:Lung Transplantation / Q000009:adverse effects*; D023421:Models, Animal; D009569:Nitric Oxide / Q000008:administration & dosage*; D009195:Peroxidase / Q000378:metabolism; D011292:Premedication; D015427:Reperfusion Injury / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D013552:Swine
D045462:Endothelium-Dependent Relaxing Factors; D016209:Interleukin-8; D009569:Nitric Oxide; D009195:Peroxidase