Low-dose nitric oxide inhalation during initial reperfusion enhances rat lung graft function.
BACKGROUND
In ischemia-reperfusion injury, the production of nitric oxide by dysfunctional endothelium falls rapidly within minutes of the onset of reperfusion. Replenishment during this critical early period using inhaled nitric oxide may benefit lung grafts through modulation of vascular tone, endothelial permeability, neutrophil and platelet function, and availability of reactive oxygen species.


METHODS
Rat lung grafts were flushed with 60 mL/kg cold University of Wisconsin solution and were reperfused either immediately (group I, n = 5) or after 24-hour 4 degrees C storage (groups II and III, n = 5 each), for 60 minutes in an ex vivo model incorporating a support animal. Graft ventilation was with room air. In group III, 20 parts per million inhaled nitric oxide was added during the initial 10 minutes of reperfusion, whereas in groups I and II, equivalent flows of nitrogen were added to standardize oxygen concentration.


RESULTS
Compared with group I, graft function in group II was poor, with reductions in oxygenation and blood flow and elevations of mean pulmonary artery pressure, peak airway pressure, and wet to dry weight ratio. In contrast, during nitric oxide inhalation in group III, graft function improved to control levels. This improvement was subsequently sustained throughout the reperfusion period.


CONCLUSIONS
Low-dose inhaled nitric oxide administration in the early phase of reperfusion of stored lung grafts can yield sustained improvement in function. There may be a role for inhaled nitric oxide in the prevention of reperfusion injury in transplanted lungs.
Bhabra
M S
MS
Department of Cardiothoracic Surgery, Wythenshawe Hospital, Manchester, United Kingdom.
Hopkinson
D N
DN
Shaw
T E
TE
Hooper
T L
TL
D000818:Animals; D001794:Blood Pressure; D006439:Hemodynamics; D016040:Lung Transplantation / Q000502:physiology*; D008297:Male; D009569:Nitric Oxide / Q000627:therapeutic use*; D011183:Postoperative Complications / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow; D015427:Reperfusion Injury / Q000517:prevention & control*
D009569:Nitric Oxide