ENHANCED PRESERVATION OF ORTHOTOPICALLY TRANSPLANTED RAT LUNGS BY NITROGLYCERIN BUT NOT HYDRALAZINE - REQUIREMENT FOR GRAFT VASCULAR HOMEOSTASIS BEYOND HARVEST VASODILATION
Y. Naka et al., ENHANCED PRESERVATION OF ORTHOTOPICALLY TRANSPLANTED RAT LUNGS BY NITROGLYCERIN BUT NOT HYDRALAZINE - REQUIREMENT FOR GRAFT VASCULAR HOMEOSTASIS BEYOND HARVEST VASODILATION, Circulation research, 76(5), 1995, pp. 900-906
Nitric oxide (NO) produced within the lungs maintains pulmonary vascul
ar homeostatic properties, modulating leukocyte traffic, platelet aggr
egation, and vasomotor tone. Because reactive oxygen intermediates gen
erated during reperfusion react rapidly with available NO, we hypothes
ized that the NO donor nitroglycerin (NTG) would enhance lung preserva
tion for transplantation by improving graft blood flow and reducing gr
aft neutrophil and platelet sequestration. By use of an orthotopic rat
left lung transplant model, with ligation of the native right pulmona
ry artery to ensure that recipient survival and physiological measurem
ents depend entirely on the transplanted lung, transplants were perfor
med in 70 male Lewis rats after 6-hour 4 degrees C preservation in Eur
o-Collins solution (EC) alone or EC with supplemental NTG. Compared wi
th EC alone, supplemental NTG significantly increased pulmonary arteri
al flow (2.2+/-1.4 to 21.4+/-2.9 mL/min, P<.01), decreased pulmonary v
ascular resistance (7.4+/-2.0 to 1.4+/-0.1x10(3) Woods units, P<.05),
improved arterial oxygenation (163+/-57 to 501+/-31 mm Hg, P<.01), and
enhanced recipient survival (17% to 100%, P<.001). These beneficial e
ffects of NTG were dose dependent over a range of 0.001 to 0.1 mg/mL.
Although NTG caused significant pulmonary vasodilation during the harv
est/flushing period, the direct-acting vasodilator hydralazine caused
greater vasodilation than did NTG but was associated with poor graft f
unction, elevated pulmonary vascular resistance, and poor recipient su
rvival. To explore nonvasodilator protective mechanisms of NTG, graft
neutrophil and platelet sequestration were studied; supplemental NTG s
ignificantly reduced both neutrophil and platelet accumulation compare
d with either hydralazine or EC alone. These findings suggest that vas
odilation alone at the lime of harvest is insufficient to protect the
lungs. NTG, which produces antineutrophil and antiplatelet effects as
well as harvest vasodilation, appears to be a simple and effective add
itive that will improve lung preservation for transplantation.