Nitroglycerin reperfusion reduces ischemia-reperfusion injury in non-heart-beating donor lungs.
BACKGROUND
Lung transplantation is severely limited by an inadequate supply of lungs from brain-dead donors. A potential solution is use of lungs from non-heart-beating donors (NHBDs) with retrieval at intervals after circulatory arrest and death. A warm ischemic period with concomitant reperfusion injury is a major limiting factor in the transplantation of lungs retrieved from NHBDs. We hypothesized that the administration of the nitric oxide-donor nitroglycerin to lungs from NHBDs would reduce ischemia-reperfusion injury by activation of guanylate cyclase to form guanosine 3',5'-cyclic monophosphate (cGMP).


METHODS
An in situ isolated perfused rat lung model was used. Lungs were retrieved from rats at varying intervals after circulatory arrest and death. Lungs were either ventilated with O(2) in situ or not ventilated. Lungs were reperfused at intervals after death with Earle's solution with or without nitroglycerin (0.1 mg/ml). Lung ischemia-reperfusion injury was assessed by capillary filtration coefficient, wet-to-dry lung weight ratio, and pulmonary hemodynamics. Tissue levels of adenine nucleotides and cGMP concentrations were measured by high-performance liquid chromatography and enzyme immunoassay, respectively.


RESULTS
Reperfusion with nitroglycerin decreased capillary filtration coefficient compared with reperfusion without nitroglycerin at all post-mortem ischemic times, irrespective of pre-harvest ventilation. cGMP levels increased significantly with nitroglycerin-reperfusion and attenuated decreases in high-energy adenine nucleotides.


CONCLUSIONS
Reperfusion of lungs with nitroglycerin may facilitate safe lung transplantation from NHBDs by reducing capillary leak after reperfusion.
Egan
Thomas M
TM
Division of Cardiothoracic Surgery, Department of Surgery, School of Medicine, University of North Carolina at Chapel Hill, 27599-7065, USA. ltxtme@med.unc.edu
Hoffmann
Steven C
SC
Sevala
Mayura
M
Sadoff
John D
JD
Schlidt
Scott A
SA
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D006152:Cyclic GMP / Q000378:metabolism; D003643:Death; D004789:Enzyme Activation; D006162:Guanylate Cyclase / Q000378:metabolism; D006439:Hemodynamics; D008168:Lung / Q000098:blood supply; D016040:Lung Transplantation; D023421:Models, Animal; D009569:Nitric Oxide / Q000502:physiology; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D005996:Nitroglycerin / Q000494:pharmacology*; D051381:Rats; D015427:Reperfusion Injury / Q000517:prevention & control*; D012121:Respiration, Artificial; D014019:Tissue Donors
D020030:Nitric Oxide Donors; D009569:Nitric Oxide; D006162:Guanylate Cyclase; D005996:Nitroglycerin; D006152:Cyclic GMP