Inhaled nitric oxide and pentoxifylline in rat lung transplantation from non-heart-beating donors. The Paris-Sud University Lung Transplantation Group.
BACKGROUND
In non-heart-beating donor lung transplantation, postmortem warm ischemia poses a special challenge. Inhaled nitric oxide and pentoxifylline have been shown to attenuate ischemia-reperfusion injury after lung transplantation. We hypothesized that concomitant administration of inhaled nitric oxide and pentoxifylline would result in a synergistic effect on ischemia-reperfusion lung injury.


METHODS
Lungs were harvested from non-heart-beating donors after 30 minutes of in situ warm ischemia, flushed, and stored for 2 hours at 4 degrees C before left lung transplantation in rats. Inhaled nitric oxide (30 ppm) was added during cadaver ventilation and reperfusion; pentoxifylline was given intravenously throughout reperfusion. The following groups were studied (n = 8 each): control, pentoxifylline, nitric oxide, and nitric oxide+pentoxifylline. Hemodynamic indices and arterial blood gases were obtained after ligation of the right pulmonary artery. Lung myeloperoxidase and wet/dry ratio were measured after death.


RESULTS
All rats that did not receive nitric oxide died within 10 minutes after ligation. Inhaled nitric oxide significantly decreased pulmonary vascular resistance and improved recipient survival. Nitric oxide + pentoxifylline improved pulmonary vascular resistance, arterial oxygen tension, and survival even further and reduced lung myeloperoxidase as compared with the group that received nitric oxide only. Preservation solution flush time was significantly decreased in both groups receiving nitric oxide, suggesting that inhaled nitric oxide used during cadaver ventilation allows for a more even distribution of the preservation solution.


CONCLUSIONS
We conclude that treatment with inhaled nitric oxide + pentoxifylline results in a synergistic protection from ischemia-reperfusion injury after non-heart-beating donor lung transplantation. This is likely the result of a dual action on the graft vasculature and neutrophil sequestration.
Murakami
S
S
Department of Thoracic and Vascular Surgery, Centre Chirurgical Marie Lannelongue, Paris-Sud University, Le Plessis Robinson, France.
Bacha
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Hervé
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Détruit
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Chapelier
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Dartevelle
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Mazmanian
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D000818:Animals; D004357:Drug Synergism; D006439:Hemodynamics / Q000187:drug effects; D008168:Lung / Q000098:blood supply; D016040:Lung Transplantation / Q000502:physiology; D008297:Male; D009504:Neutrophils / Q000187:drug effects; D009569:Nitric Oxide / Q000627:therapeutic use*; D010431:Pentoxifylline / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000627:therapeutic use*
D014665:Vasodilator Agents; D009569:Nitric Oxide; D010431:Pentoxifylline