Prevention of reperfusion injury by inhaled nitric oxide in lungs harvested from non-heart-beating donors. Paris-Sud University Lung Transplantation Group.
BACKGROUND
In lung transplantation using non-heart-beating donors (NHBD), the postmortem period of warm ischemia exacerbates lung ischemia-reperfusion injury. We hypothesized that inhaled nitric oxide (NO) would reduce ischemia-reperfusion injury, and thus ameliorate the viability of the lung graft.


METHODS
A blood-perfused, isolated rat lung model was used. Lungs were flushed and harvested from non-heart-beating donors after 30 minutes of in situ warm ischemia. The lung was then stored for 2 hours at 4 degrees C. Inhaled NO at 30 ppm was given either during the period of warm ischemia, during reperfusion, or during both periods. Lung ischemia-reperfusion injury was assessed after 1 hour of reperfusion by measuring pulmonary vascular resistance, coefficient of filtration, wet-to-dry lung weight ratio, and myeloperoxidase activity.


RESULTS
A severe IR injury occurred in lungs undergoing ischemia and reperfusion without NO as evidenced by high values of pulmonary vascular resistance (6.83 +/- 0.36 mm Hg. mL-1.min-1), coefficient of filtration (3.02 +/- 0.35 mL.min-1.cm H2O-1 x 100 g-1), and wet-to-dry lung weight ratio (8.07 +/- 0.45). Lower values (respectively, 3.31 +/- 0.44 mm Hg.mL-1.min-1, 1.49 +/- 0.34 mL.min-1.cm H2O-1 x 100 g-1, and 7.44 +/- 0.43) were observed when lungs were ventilated with NO during ischemia. Lung function was further improved when NO was given during reperfusion only. All measured variables, including myeloperoxidase activity were significantly improved when NO was given during both ischemia and reperfusion. Myeloperoxidase activity was significantly correlated with coefficient of filtration (r = 0.465; p < 0.05).


CONCLUSIONS
These data suggest that inhaled NO significantly reduces ischemia-reperfusion injury in lungs harvested from non-heart-beating donors. This effect might be mediated by inhibition of neutrophil sequestration in the reperfused lung.
Murakami
S
S
Laboratoire de Chirurgie Expérimentale, Centre Chirurgical Marie-Lannelongue, Paris-Sud University, Le Plessis Robinson, France.
Bacha
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EA
Hervé
P
P
Détruit
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H
Chapelier
A R
AR
Dartevelle
P G
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Mazmanian
G M
GM
D000280:Administration, Inhalation; D000818:Animals; D001794:Blood Pressure; D002199:Capillary Permeability; D008168:Lung / Q000098:blood supply / Q000201:enzymology / Q000473:pathology; D016040:Lung Transplantation; D008297:Male; D009569:Nitric Oxide / Q000008:administration & dosage*; D009926:Organ Preservation; D009929:Organ Size; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*; D014019:Tissue Donors; D014655:Vascular Resistance
D009569:Nitric Oxide; D009195:Peroxidase