HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Krishnadasan, B. Articles by Mulligan, M. S. Search for Related Content PubMed PubMed Citation Articles by Krishnadasan, B. Articles by Mulligan, M. S. Related Collections Lung - transplantation

J Thorac Cardiovasc Surg 2002;123:756-767
© 2002 The American Association for Thoracic Surgery

Cardiopulmonary Support and Physiology (CSP)

Decreased lung ischemia-reperfusion injury in rats after preoperative administration of cyclosporine and tacrolimus

From the Division of Cardiothoracic Surgery, University of Washington, Seattle, Wash.

Received for publication June 28, 2001. Revisions requested Aug 13, 2001; revisions received Aug 23, 2001. Accepted for publication Aug 30, 2001. Address for reprints: M. S. Mulligan, MD, Division of Cardiothoracic Surgery, 1959 NE Pacific St, University of Washington Medical Center, Seattle, WA 98195 (E-mail: msmmd{at}u.washington.edu).

Objectives: Calcineurin inhibitors reduce experimental reperfusion injury in the liver, brain, heart, kidney, and small bowel. These studies were undertaken to determine whether these agents are similarly protective against lung ischemia-reperfusion injury.
Methods: Left lungs of male rats were rendered ischemic for 90 minutes and reperfused for as long as 4 hours. Treated animals received cyclosporine A (INN: ciclosporin; 1 or 5 mg/kg) or tacrolimus (0.2 mg/kg) 6 hours before ischemia, at reperfusion, or 2 hours after reperfusion. Injury was quantitated in terms of tissue polymorphonuclear leukocyte accumulation (myeloperoxidase content), vascular permeability (iodine 125-labeled bovine serum albumin extravasation), and bronchoalveolar lavage leukocyte content. Separate tissue samples were processed for nuclear protein and cytokine messenger RNA.
Results: Treatment with cyclosporine (5 mg/kg) or tacrolimus (0.2 mg/kg) 6 hours before reperfusion reduced lung vascular permeability by 54% and 56% relative to control animals (P < .03). The protective effects of cyclosporine and tacrolimus treatment before reperfusion correlated with 42% and 43% reductions in tissue polymorphonuclear leukocyte (myeloperoxidase) content (P < .008) and marked reductions in bronchoalveolar lavage leukocyte accumulation (P < .01). Administration of cyclosporine or tacrolimus at the time of reperfusion or 2 hours into the reperfusion period offered little or no protection. Animals treated before reperfusion also demonstrated marked reductions in nuclear factor B activation and expression of proinflammatory cytokine messenger RNA.
Conclusion: Cyclosporine and tacrolimus treatment before reperfusion was protective against lung ischemia-reperfusion injury in rats. The mechanism of these protective effects may involve the inhibition of nuclear factor B, a central transcription factor mediating inflammatory injury. The decreased expression of cytokine messenger RNA indicates that both cyclosporine and tacrolimus may exert their protective effects at the pretranscriptional level.

This article has been cited by other articles:

				M. Sugita, Y. Berthiaume, M. VanSpall, A. Dagenais, and P. Ferraro Pharmacologic modulation of alveolar liquid clearance in transplanted lungs by phentolamine and FK506. Ann. Thorac. Surg., September 1, 2009; 88(3): 958 - 964. [Abstract] [Full Text] [PDF]

				Z. Yang, A. K. Sharma, J. Linden, I. L. Kron, and V. E. Laubach CD4+ T lymphocytes mediate acute pulmonary ischemia-reperfusion injury. J. Thorac. Cardiovasc. Surg., March 1, 2009; 137(3): 695 - 702. [Abstract] [Full Text] [PDF]

				N. P. van der Kaaij, J. Kluin, J. J. Haitsma, M. A. den Bakker, B. N. Lambrecht, B. Lachmann, R. W.F. de Bruin, and A. J.J.C. Bogers Surfactant pretreatment decreases long-term damage after ischemia-reperfusion injury of the lung Eur. J. Cardiothorac. Surg., February 1, 2009; 35(2): 304 - 312. [Abstract] [Full Text] [PDF]

				N. P. van der Kaaij, J. J. Haitsma, J. Kluin, B. N. Lambrecht, B. Lachmann, R. W.F. de Bruin, and A. J.J.C. Bogers Surfactant pretreatment ameliorates ischemia-reperfusion injury of the lung Eur. J. Cardiothorac. Surg., May 1, 2005; 27(5): 774 - 782. [Abstract] [Full Text] [PDF]

				B. V. Naidu, S. M. Woolley, A. S. Farivar, R. Thomas, C. H. Fraga, C. H. Goss, and M. S. Mulligan Early tumor necrosis factor-{alpha} release from the pulmonary macrophage in lung ischemia-reperfusion injury J. Thorac. Cardiovasc. Surg., May 1, 2004; 127(5): 1502 - 1508. [Abstract] [Full Text] [PDF]

				K. Ito, J. Shimada, D. Kato, S. Toda, T. Takagi, Y. Naito, T. Yoshikawa, and N. Kitamura Protective effects of preischemic treatment with pioglitazone, a peroxisome proliferator-activated receptor-{gamma} ligand, on lung ischemia-reperfusion injury in rats Eur. J. Cardiothorac. Surg., April 1, 2004; 25(4): 530 - 536. [Abstract] [Full Text] [PDF]

				S. M. Woolley, A. S. Farivar, B. V. Naidu, M. Rosengart, R. Thomas, C. Fraga, and M. S. Mulligan Endotracheal calcineurin inhibition ameliorates injury in an experimental model of lung ischemia-reperfusion J. Thorac. Cardiovasc. Surg., February 1, 2004; 127(2): 376 - 384. [Abstract] [Full Text] [PDF]

				B. V. Naidu, S. M. Woolley, A. S. Farivar, R. Thomas, C. Fraga, and M. S. Mulligan Simvastatin ameliorates injury in an experimental model of lung ischemia-reperfusion J. Thorac. Cardiovasc. Surg., August 1, 2003; 126(2): 482 - 489. [Abstract] [Full Text] [PDF]

				B. V. Naidu, B. Krishnadasan, A. S. Farivar, S. M. Woolley, R. Thomas, N. Van Rooijen, E. D. Verrier, and M. S. Mulligan Early activation of the alveolar macrophage is critical to the development of lung ischemia-reperfusion injury J. Thorac. Cardiovasc. Surg., July 1, 2003; 126(1): 200 - 207. [Abstract] [Full Text] [PDF]

				D. A. Bull and J. Maurer Aprotinin and preservation of myocardial function after ischemia-reperfusion injury Ann. Thorac. Surg., February 1, 2003; 75(2): S735 - 739. [Abstract] [Full Text] [PDF]

				B. V. Naidu, B. Krishnadasan, K. Byrne, A. L. Farr, M. Rosengart, E. D. Verrier, and M. S. Mulligan Regulation of chemokine expression by cyclosporine a in alveolar macrophages exposed to hypoxia and reoxygenation Ann. Thorac. Surg., September 1, 2002; 74(3): 899 - 905. [Abstract] [Full Text] [PDF]