Superior protection in orthotopic rat lung transplantation with cyclic adenosine monophosphate and nitroglycerin-containing preservation solution

Background: Primary lung graft failure is common, and current lung preserva tion strategies are suboptimal. Because the decline in lung levels of cycli c adenosine monophosphate and cyclic guanosine monophosphate during preserv ation could enhance adhesiveness of endothelial cells for leukocytes as wel l as increase vascular permeability and vasoconstriction, we hypothesized t hat buttressing these levels by means of a preservation solution would sign ificantly improve lung preservation. Methods: An orthotopic rat left lung t ransplantation model was used. Lungs were harvested from male Lewis rats an d preserved for 6 hours at 4 degrees C with (1) Euro-Collins solution (n = 8); (2) University of Wisconsin solution (n = 8); (3) low-potassium dextran glucose solution (n = 8); (4) Columbia University solution (n = 8), which contains a cyclic adenosine monophosphate analog (dibutyryl cyclic adenosin e monophosphate) and a nitric oxide donor (nitroglycerin) to buttress cycli c guanosine monophosphate levels; or (5) Columbia University solution witho ut cyclic adenosine monophosphate or nitroglycerin (n = 8). PaO2, pulmonary vascular resistance, and recipient survival were evaluated 30 minutes afte r left lung transplantation and removal of the nontransplanted right lung f rom the pulmonary circulation. Results: Among all groups studied, grafts st ored with Columbia University solution demonstrated the highest PaO2 (355 /- 25 mm Hg for Columbia University solution versus 95 +/- 22 mm Hg for Eur o-Collins solution, P < .01, 172 +/- 55 mm Hg for University of Wisconsin s olution, P < .05, 76 +/- 15 mm Hg for low-potassium dextran glucose solutio n, P < .01, and 82 +/- 25 mm Hg for Columbia University solution without cy clic adenosine monophosphate or nitroglycerin, P < .01) and the lowest pulm onary vascular resistances (1 +/- 0.2 mm Hg mL(-1).min(-1) for Columbia Uni versity solution versus 12 +/- 4 mm Hg.mL(-1).min(-1) for Euro-Collins solu tion, P < .01, 9 +/- 2 mm Hg mL(-1).min(-1) for University of Wisconsin sol ution, 14 +/- 6 mm Hg.mL(-1).min(-1) for low-potassium dextran glucose solu tion, P < .01, and 8 +/- 2 mm Hg.mL(-1).min(-1) for Columbia University sol ution without cyclic adenosine monophosphate and nitroglycerin). These func tional and hemodynamic improvements provided by Columbia University solutio n were accompanied by decreased graft leukostasis and decreased recipient t umor necrosis factor alpha and interleukin 1 alpha levels compared with the other groups. In tote, these improvements translated into superior surviva l among recipients of Columbia University solution-preserved grafts (100% f or Columbia University solution, 37% for Euro-Collins solution, P < .01, 50 % for University of Wisconsin solution, P < .05, 50% for low-potassium dest ran glucose solution, P < .05, and 13% for Columbia University solution wit hout cyclic adenosine monophosphate and nitroglycerin, P < .01). Conclusion : Nitroglycerin and cyclic adenosine monophosphate confer beneficial vascul ar effects that make Columbia University solution a superior lung preservat ion solution in a stringent rat lung transplantation model.