Enhanced preservation of orthotopically transplanted rat lungs by nitroglycerin but not hydralazine

Requirement for graft vascular homeostasis beyond harvest vasodilation

Y. Naka, N. C. Chowdhury, H. Liao, D. K. Roy, M. C. Oz, Robert E. Michler, D. J. Pinsky

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

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°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 103 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. These findings suggest that vasodilation alone at the time 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 additive that will improve lung preservation for transplantation.

Original languageEnglish (US)
Pages (from-to)900-906
Number of pages7
JournalCirculation Research
Volume76
Issue number5
StatePublished - 1995
Externally publishedYes

Fingerprint

Hydralazine
Nitroglycerin
Vasodilation
Blood Vessels
Homeostasis
Transplants
Lung
Neutrophils
Blood Platelets
Lung Transplantation
Vascular Resistance
Nitric Oxide
Nitric Oxide Donors
Vasodilator Agents
Platelet Aggregation
Pulmonary Artery
Reperfusion
Ligation
Leukocytes
Oxygen

Keywords

  • harvest vasodilation
  • hydralazine
  • lung transplantation
  • nitroglycerin

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Enhanced preservation of orthotopically transplanted rat lungs by nitroglycerin but not hydralazine : Requirement for graft vascular homeostasis beyond harvest vasodilation. / Naka, Y.; Chowdhury, N. C.; Liao, H.; Roy, D. K.; Oz, M. C.; Michler, Robert E.; Pinsky, D. J.

In: Circulation Research, Vol. 76, No. 5, 1995, p. 900-906.

Research output: Contribution to journalArticle

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