| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 1995 American Heart Association, Inc.
Articles |
Enhanced Preservation of Orthotopically Transplanted Rat Lungs by Nitroglycerin but Not Hydralazine
Requirement for Graft Vascular Homeostasis Beyond Harvest Vasodilation
From the Departments of Physiology (Y.N., H.L.), Surgery (N.C.C., D.K.R., M.C.O., R.E.M.), and Medicine (D.J.P.), Columbia University College of Physicians and Surgeons, New York, NY.
Correspondence to David J. Pinsky, MD, Department of Medicine, Columbia University College of Physicians and Surgeons, 630 West 168th St, New York, NY 10032.
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±0.1x103 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.
Key Words: nitroglycerin • hydralazine • lung transplantation • harvest vasodilation
This article has been cited by other articles:
 |
|
 |
|
  Y. Toyoda, J. Thacker, R. Santos, D. Nguyen, J. Bhama, C. Bermudez, R. Kormos, B. Johnson, M. Crespo, J. Pilewski, et al. Long-Term Outcome of Lung and Heart-Lung Transplantation for Idiopathic Pulmonary Arterial Hypertension Ann. Thorac. Surg., October 1, 2008; 86(4): 1116 - 1122. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. I. Sternberg, D. Shimbo, S. M. Kawut, J. Sarkar, G. Hurlitz, F. D'Ovidio, D. J. Lederer, J. S. Wilt, S. M. Arcasoy, D. J. Pinsky, et al. Platelet activation in the postoperative period after lung transplantation J. Thorac. Cardiovasc. Surg., March 1, 2008; 135(3): 679 - 684. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Wittwer, J. M. Albes, A. Fehrenbach, T. Pech, U. F. W. Franke, J. Richter, and T. Wahlers Experimental lung preservation with Perfadex: Effect of the NO-donor nitroglycerin on postischemic outcome J. Thorac. Cardiovasc. Surg., June 1, 2003; 125(6): 1208 - 1216. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. O. Meade, J. T. Granton, A. Matte-Martyn, K. McRae, B. Weaver, P. Cripps, and S. H. Keshavjee A Randomized Trial of Inhaled Nitric Oxide to Prevent Ischemia-Reperfusion Injury after Lung Transplantation Am. J. Respir. Crit. Care Med., June 1, 2003; 167(11): 1483 - 1489. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. de Perrot, M. Liu, T. K. Waddell, and S. Keshavjee Ischemia-Reperfusion-induced Lung Injury Am. J. Respir. Crit. Care Med., February 15, 2003; 167(4): 490 - 511. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. R. Karamsetty and J. R. Klinger NO: More Than Just a Vasodilator in Lung Transplantation Am. J. Respir. Cell Mol. Biol., January 1, 2002; 26(1): 1 - 5. [Full Text] [PDF]
|
|
|
|
|
|
K. Minamoto, D. J. Pinsky, T. Fujita, and Y. Naka Timing of Nitric Oxide Donor Supplementation Determines Endothelin-1 Regulation and Quality of Lung Preservation for Transplantation Am. J. Respir. Cell Mol. Biol., January 1, 2002; 26(1): 14 - 21. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Schutte, M. Witzenrath, K. Mayer, N. Weissmann, A. Schell, S. Rosseau, W. Seeger, and F. Grimminger The PDE inhibitor zaprinast enhances NO-mediated protection against vascular leakage in reperfused lungs Am J Physiol Lung Cell Mol Physiol, September 1, 2000; 279(3): L496 - L502. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Bando, J. M. Albes, J. Schone, H. Wada, S. Hitomi, T. Wahlers, and H.-J. Schafers Significance of cyclic adenosine monophosphate and nitroglycerin in ET-Kyoto solution for lung preservation Ann. Thorac. Surg., March 1, 2000; 69(3): 887 - 891. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Pinsky and Y. Naka Ann. Thorac. Surg., March 1, 2000; 69(3): 891 - 892. [Full Text] [PDF]
|
|
|
|
|
|
M. KAWASHIMA, T. BANDO, T. NAKAMURA, N. ISOWA, M. LIU, S. TOYOKUNI, S. HITOMI, and H. WADA Cytoprotective Effects of Nitroglycerin in Ischemia-Reperfusion-Induced Lung Injury Am. J. Respir. Crit. Care Med., March 1, 2000; 161(3): 935 - 943. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Toda, K. Kayano, A. Karimova, Y. Naka, T. Fujita, K. Minamoto, C. Y. Wang, and D. J. Pinsky Antisense Intercellular Adhesion Molecule-1 (ICAM-1) Oligodeoxyribonucleotide Delivered During Organ Preservation Inhibits Posttransplant ICAM-1 Expression and Reduces Primary Lung Isograft Failure Circ. Res., February 4, 2000; 86(2): 166 - 174. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Kayano, K. Toda, Y. Naka, K. Okada, M. C. Oz, and D. J. Pinsky SUPERIOR PROTECTION IN ORTHOTOPIC RAT LUNG TRANSPLANTATION WITHCYCLIC ADENOSINE MONOPHOSPHATE AND NITROGLYCERIN-CONTAINING PRESERVATIONSOLUTION J. Thorac. Cardiovasc. Surg., July 1, 1999; 118(1): 135 - 144. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. F. Choudhri, B. L. Hoh, C. J. Prestigiacomo, J. Huang, L. J. Kim, A. M. Schmidt, W. Kisiel, E. S. Connolly Jr., and D. J. Pinsky Targeted Inhibition of Intrinsic Coagulation Limits Cerebral Injury in Stroke without Increasing Intracerebral Hemorrhage J. Exp. Med., July 1, 1999; 190(1): 91 - 100. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Licker, A. Schweizer, L. Hohn, D. R Morel, and A. Spiliopoulos Single lung transplantation for adult respiratory distress syndrome after paraquat poisoning Thorax, July 1, 1998; 53(7): 620 - 621. [Abstract] [Full Text]
|
|
|
|
 |
|
 S. C. Body and S. K. Shernan The Utility of Nitric Oxide in the Postoperative Period Seminars in Cardiothoracic and Vascular Anesthesia, March 1, 1998; 2(1): 4 - 30. [Abstract] [PDF]
|
|
|
|
|
|
S. MURAKAMI, E. A. BACHA, G. M. MAZMANIAN, H. DÉTRUIT, A. CHAPELIER, P. DARTEVELLE, and P. HERVÉ Effects of Various Timings and Concentrations of Inhaled Nitric Oxide in Lung Ischemia-Reperfusion Am. J. Respir. Crit. Care Med., July 1, 1997; 156(2): 454 - 458. [Abstract] [Full Text]
|
|
|
|
|
|
M. S. Bhabra, D. N. Hopkinson, T. E. Shaw, and T. L. Hooper Low-Dose Nitric Oxide Inhalation During Initial Reperfusion Enhances Rat Lung Graft Function Ann. Thorac. Surg., February 1, 1997; 63(2): 339 - 344. [Abstract] [Full Text]
|
|
|
|
|
|
M. S. Bhabra, D. N. Hopkinson, T. E. Shaw, and T. L. Hooper ATTENUATION OF LUNG GRAFT REPERFUSION INJURY BY A NITRIC OXIDE DONOR J. Thorac. Cardiovasc. Surg., February 1, 1997; 113(2): 327 - 334. [Abstract] [Full Text]
|
|
|
|
 |
|
 Y. Naka, K. Toda, K. Kayano, M. C. Oz, and D. J. Pinsky Failure to express the P-selectin gene or P-selectin blockade confers early pulmonary protection after lung ischemia or transplantation PNAS, January 21, 1997; 94(2): 757 - 761. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-T. LU, S. F. LIU, J. A. MITCHELL, A. B. MALIK, P. G. HELLEWELL, and T. W. EVANS The Role of Endogenous Nitric Oxide in Modulating Ischemia-Reperfusion Injury in the Isolated, Blood-perfused Rat Lung Am. J. Respir. Crit. Care Med., January 1, 1997; 157(1): 273 - 279. [Abstract] [Full Text]
|
|
|
|
|
|
M. S. Bhabra, D. N. Hopkinson, T. E. Shaw, and T. L. Hooper Relative Importance of Prostaglandin/Cyclic Adenosine Monophosphate and Nitric Oxide/Cyclic Guanosine Monophosphate Pathways in Lung Preservation Ann. Thorac. Surg., November 1, 1996; 62(5): 1494 - 1499. [Abstract] [Full Text]
|
|
|
|
|
|
Y. Naka, D. K. Roy, H. Liao, N. C. Chowdhury, R. E. Michler, M. C. Oz, and D. J. Pinsky cAMP-Mediated Vascular Protection in an Orthotopic Rat Lung Transplant Model: Insights Into the Mechanism of Action of Prostaglandin E1 to Improve Lung Preservation Circ. Res., October 1, 1996; 79(4): 773 - 783. [Abstract] [Full Text]
|
|
|
|
|
|
E. A. Bacha, P. Herve, S. Murakami, A. Chapelier, G.-M. Mazmanian, V. de Montpreville, H. Detruit, J.-M. Libert, P. Dartevelle, and P.-S. U. L. T. Group LASTING BENEFICIAL EFFECT OF SHORT-TERM INHALED NITRIC OXIDE ON GRAFT FUNCTION AFTER LUNG TRANSPLANTATION J. Thorac. Cardiovasc. Surg., September 1, 1996; 112(3): 590 - 598. [Abstract] [Full Text]
|
|
|
|
|
|
R. J. Novick, K. E. Gehman, I. S. Ali, and J. Lee Lung Preservation: The Importance of Endothelial and Alveolar Type II Cell Integrity Ann. Thorac. Surg., July 1, 1996; 62(1): 302 - 314. [Abstract] [Full Text]
|
|
|
|
|
|
Y. Naka, D. K. Roy, A. J. Smerling, R. E. Michler, C. R. Smith, D. M. Stern, M. C. Oz, and D. J. Pinsky INHALED NITRIC OXIDE FAILS TO CONFER THE PULMONARY PROTECTION PROVIDED BY DISTAL STIMULATION OF THE NITRIC OXIDE PATHWAY AT THE LEVEL OF CYCLIC GUANOSINE MONOPHOSPHATE J. Thorac. Cardiovasc. Surg., November 1, 1995; 110(5): 1434 - 1441. [Abstract] [Full Text]
|
|