Nitroglycerin maintains graft vascular homeostasis and enhances preservation in an orthotopic rat lung transplant model.
Transplanted lungs often fail during the peritransplantation period for poorly understood reasons. Because the nitric oxide pathway regulates pulmonary vascular tone, helps to maintain the integrity of the endothelial barrier, and modulates neutrophil adhesivity and activation, we hypothesized that perturbation of this pathway during the preservation and reperfusion of transplanted lungs might play a critical role in mediating early graft failure. To evaluate whether supplementing the preservation solution with the nitric oxide donor nitroglycerin enhances lung preservation for transplantation, we obtained hemodynamic measurements in a model of orthotopic left lung transplantation in the rat after ligation of the native right pulmonary artery. In these experiments, recipient survival and hemodynamics depended solely on the transplanted lung. The left lung was harvested from 22 rats, flushed with either lactated Ringer's solution alone (control, n = 11) or Ringer's solution supplemented with nitroglycerin (0.1 mg/ml, n = 11), preserved for 4 hours at 4 degrees C, and then transplanted using a rapid cuff technique for bronchial and vascular anastomoses. Nitroglycerin significantly improved arterial blood oxygenation (339 +/- 66 versus 130 +/- 12 mm Hg, p < 0.05), increased pulmonary arterial flow (7.6 +/- 1.9 versus 0.9 +/- 0.2 ml/min, p < 0.005), decreased pulmonary vascular resistance (1.7 +/- 0.4 versus 6.6 +/- 1.9 x 10(3) Wood units, p < 0.05), and enhanced recipient survival (64% versus 0%, p < 0.05). Control grafts had significantly greater neutrophil accumulation (50% greater as quantified by myeloperoxidase activity, p < 0.05) than grafts preserved in the presence of nitroglycerin. These studies show that supplementation of the preservation solution with the nitric oxide donor nitroglycerin maintains graft vascular homeostasis and significantly improves pulmonary function and recipient survival after transplantation.
Naka
Y
Y
Department of Physiology, Columbia University College of Physicians and Surgeons, New York, N.Y.
Chowdhury
N C
NC
Oz
M C
MC
Smith
C R
CR
Yano
O J
OJ
Michler
R E
RE
Stern
D M
DM
Pinsky
D J
DJ
D000818:Animals; D006085:Graft Survival / Q000187:drug effects*; D006706:Homeostasis / Q000187:drug effects; D007552:Isotonic Solutions / Q000494:pharmacology; D016040:Lung Transplantation / Q000379:methods / Q000502:physiology*; D008297:Male; D005996:Nitroglycerin / Q000494:pharmacology*; D009926:Organ Preservation / Q000379:methods*; D011651:Pulmonary Artery / Q000187:drug effects; D011652:Pulmonary Circulation / Q000187:drug effects*; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D011667:Pulmonary Veins / Q000187:drug effects; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000517:prevention & control*; D000077325:Ringer's Lactate
D007552:Isotonic Solutions; D000077325:Ringer's Lactate; D005996:Nitroglycerin