Enhanced preservation of orthotopically transplanted rat lungs by nitroglycerin but not hydralazine. Requirement for graft vascular homeostasis beyond harvest vasodilation.
Nitric oxide (NO) produced within the lungs maintains pulmonary vascular homeostatic properties, modulating leukocyte traffic, platelet aggregation, and vasomotor tone. Because reactive oxygen intermediates generated during reperfusion react rapidly with available NO, we hypothesized that the NO donor nitroglycerin (NTG) would enhance lung preservation for transplantation by improving graft blood flow and reducing graft neutrophil and platelet sequestration. By use of an orthotopic rat left lung transplant model, with ligation of the native right pulmonary artery to ensure that recipient survival and physiological measurements depend entirely on the transplanted lung, transplants were performed in 70 male Lewis rats after 6-hour 4 degrees C preservation in Euro-Collins solution (EC) alone or EC with supplemental NTG. Compared with EC alone, supplemental NTG significantly increased pulmonary arterial flow (2.2 +/- 1.4 to 21.4 +/- 2.9 mL/min, P < .01), decreased pulmonary vascular resistance (7.4 +/- 2.0 to 1.4 +/- 0.1 x 10(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 effects of NTG were dose dependent over a range of 0.001 to 0.1 mg/mL. Although NTG caused significant pulmonary vasodilation during the harvest/flushing period, the direct-acting vasodilator hydralazine caused greater vasodilation than did NTG but was associated with poor graft function, elevated pulmonary vascular resistance, and poor recipient survival. To explore nonvasodilator protective mechanisms of NTG, graft neutrophil and platelet sequestration were studied; supplemental NTG significantly reduced both neutrophil and platelet accumulation compared with either hydralazine or EC alone.(ABSTRACT TRUNCATED AT 250 WORDS)
Naka
Y
Y
Department of Physiology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Chowdhury
N C
NC
Liao
H
H
Roy
D K
DK
Oz
M C
MC
Michler
R E
RE
Pinsky
D J
DJ
D000818:Animals; D006084:Graft Rejection / Q000517:prevention & control; D006085:Graft Survival; D006830:Hydralazine / Q000627:therapeutic use*; D008168:Lung / Q000098:blood supply; D016040:Lung Transplantation; D008297:Male; D005996:Nitroglycerin / Q000627:therapeutic use*; D051381:Rats; D011917:Rats, Inbred Lew
D006830:Hydralazine; D005996:Nitroglycerin