Inhaled nitric oxide for modulation of ischemia-reperfusion injury in lung transplantation.
BACKGROUND
The prophylactic administration of inhaled nitric oxide (NO) during reperfusion after lung transplantation has been shown to reduce neutrophil-induced injury in animal models. There remain questions regarding efficacy in the clinical setting and concerns regarding increased free radical injury. We sought to assess the efficacy of NO in reducing neutrophil infiltration and associated injury if administered from the very onset of reperfusion in clinical lung transplantation.


METHODS
Twenty bilateral sequential lung transplant recipients were randomized to receive 20-ppm inhaled NO (NO group) or a standard anesthetic gas mixture (control group) from the onset of ventilation. Bronchoalveolar lavage was performed immediately prior to implantation and after 30 minutes of reperfusion and analyzed for inflammatory cytokine levels and free radical surrogates. Primary graft dysfunction (PGD) scoring was performed prospectively for 72 hours post-transplant.


RESULTS
The prophylactic administration of NO during the first 30 minutes of reperfusion had no statistically significant effect on the development of Grade II to III PGD (5 of 10 in NO group and 7 of 10 in control group, p = 0.36) or gas exchange (area under the curve: 429 +/- 296 vs 336 +/- 306; p = 0.64) in the NO and control groups, respectively. Pulmonary neutrophil sequestration, as measured by the transpulmonary arteriovenous neutrophil difference, was not influenced by the administration of NO. Prophylactic NO did not significantly alter the concentration of interleukin-8, myeloperoxidase or nitrotyrosine during transplantation.


CONCLUSIONS
This study could not demonstrate a significant effect of inhaled NO during the first 30 minutes of reperfusion in the prevention of neutrophil injury and primary graft dysfunction after lung transplantation.
Botha
Phil
P
Department of Cardiopulmonary Transplantation, Freeman Hospital, High Heaton, Newcastle upon Tyne, UK. p.botha@ncl.ac.uk
Jeyakanthan
Mylvaganam
M
Rao
Jagan N
JN
Fisher
Andrew J
AJ
Prabhu
Mahesh
M
Dark
John H
JH
Clark
Steven C
SC
D000280:Administration, Inhalation; D000328:Adult; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D005260:Female; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000627:therapeutic use*; D005609:Free Radicals / Q000378:metabolism; D006084:Graft Rejection / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D016209:Interleukin-8 / Q000032:analysis / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D016040:Lung Transplantation / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000473:pathology; D009569:Nitric Oxide / Q000008:administration & dosage / Q000627:therapeutic use*; D009195:Peroxidase / Q000378:metabolism; D015427:Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D016166:Free Radical Scavengers; D005609:Free Radicals; D016209:Interleukin-8; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D009195:Peroxidase