Protective effects of inhaled nitric oxide and gabexate mesilate in lung reperfusion injury after transplantation from non-heart-beat donors.
BACKGROUND
The use of lung grafts from non-heart-beat donors (NHBDs) is one way of solving the critical donor organ shortage. Inhaled nitric oxide (NO) and gabexate mesilate (FOY), a protease inhibitor, can attenuate some types of neutrophil-mediated tissue injury. Using an isolated lung ventilation and perfusion model, we studied the effects of these agents on reperfusion injury following lung transplantation from NHBDs.


METHODS
Five groups of minipigs were studied. In group 1(n = 6), the lungs were flushed and harvested after cardiac arrest, and were reperfused for 2 hours after 2 hours of cold ischemia. In group 2 (n = 6), the lungs were harvested after 2 hours of in situ warm ischemia, followed by 2 hours of cold ischemia and 2 hours of reperfusion. In groups 3 (n = 7), 4 (n = 7), and 5 (n = 6), the procedure was the same as in group 2, except in group 3, NO was inhaled before and after ischemia, in group 4, FOY was given intravenously, and in group 5, a combination of inhaled NO and intravenous FOY were administered.


RESULTS
Compared with group 1, group 2 had higher mean pulmonary arterial pressure, vascular resistance, and lower arterial blood oxygen tension. Furthermore, these negative effects of warm ischemia were also reflected in the contents of bronchoalveolar lavage fluid, tissue myeloperoxidase (MPO) activity, histology, and permeability change. Either FOY or NO administration (groups 3 or 4) ameliorated the associated injury. A combination of FOY and NO use (group5) decreased the parameters of lung reperfusion injury measurement to a larger degree than either agent individually.


CONCLUSIONS
The inhaled NO and FOY can protect NHBD lung grafts at an early reperfusion period. Their use in combination has an additive protective effect that might be applied to the protection of NHBD grafts from preservation and reperfusion injury.
Luh
Shi Ping
SP
Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan, Republic of China.
Tsai
Chen Cheng
CC
Shau
Wen Yi
WY
Shiau
Shoei Yn Lin
SY
Jan
I Shiow
IS
Kuo
Sow Hsong
SH
Yang
Pan Chyr
PC
D000280:Administration, Inhalation; D000818:Animals; D001784:Blood Gas Analysis; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002199:Capillary Permeability / Q000187:drug effects; D004359:Drug Therapy, Combination; D016670:Gabexate / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016027:Heart Transplantation; D008168:Lung / Q000098:blood supply*; D055370:Lung Injury; D016040:Lung Transplantation; D020556:Neutrophil Infiltration / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects; D009569:Nitric Oxide / Q000493:pharmacokinetics / Q000627:therapeutic use*; D009195:Peroxidase / Q000187:drug effects; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D015427:Reperfusion Injury / Q000097:blood / Q000517:prevention & control*; D013556:Swine, Miniature; D013997:Time Factors; D014019:Tissue Donors; D014655:Vascular Resistance / Q000187:drug effects
D009569:Nitric Oxide; D016670:Gabexate; D009195:Peroxidase