JTCS Email Content Delivery
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

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

J Thorac Cardiovasc Surg 2003;126:482-489
© 2003 The American Association for Thoracic Surgery

Cardiothoracic transplantation

Simvastatin ameliorates injury in an experimental model of lung ischemia-reperfusion

Babu V. Naidu, FRCSa, Steven M. Woolley, MRCSa, Alexander S. Farivar, MDa, Robert Thomas, BAa, Charles Fraga, MSca, Michael S. Mulligan, MD, FACSa,*

a Division of Cardiothoracic Surgery, University of Washington, Seattle, Wash, USA

Read at the Twenty-seventh Annual Meeting of The Western Thoracic Surgical Association, Big Sky, Mont, June 19-22, 2002.

Received for publication June 28, 2002; revisions received August 19, 2002; revisions received December 13, 2002; accepted for publication January 14, 2003.

* Address for reprints: Michael S. Mulligan, MD, FACS, Box 356310, University of Washington, 1959 NE Pacific St, Seattle, WA 98195, USA
msmmd{at}u.washington.edu

OBJECTIVES: Statins are lipid-lowering drugs with anti-inflammatory and antioxidant properties. This study explores the potential of these commonly prescribed agents to ameliorate lung ischemia-reperfusion injury.

METHODS: Left lungs of Long-Evans rats were rendered ischemic for 90 minutes and reperfused for up to 4 hours. Treated animals received simvastatin orally (0.5 mg/kg) for 5 days before the experiment. Injury was quantitated in terms of tissue myeloperoxidase content, vascular permeability (125I bovine serum albumin extravasation), and bronchoalveolar lavage leukocyte and cytokine content. Changes in nuclear translocation of transcription factors were evaluated by electromobility shift assay. Additional animals received NG-nitro-L-arginine methyl ester before ischemia-reperfusion to assess whether inhibition of nitric oxide synthase could reverse simvastatin's protective effects. The presence of nicotinamide adenine dinucleotide phosphate oxidase was also evaluated using enzyme staining both histologically and in native electrophoresis.

RESULTS: Lung vascular permeability was reduced in treated animals by 71% compared with positive controls (P < .001). Administration of NG-nitro-L-arginine methyl ester reversed this protection. The protective effects of statin pretreatment correlated with a 68% reduction in tissue myeloperoxidase content (P < .01), marked reductions in bronchoalveolar lavage leukocyte accumulation, and decreased expression of proinflammatory cytokines. Nicotinamide adenine dinucleotide phosphate oxidase expression also decreased with statin treatment.

CONCLUSION: In addition to its antioxidant properties, the protective effects of simvastatin are likely mediated by modulation of endothelial nitric oxide synthase. The potential to pretreat recipients of lung transplantation with statins to ameliorate reperfusion injury is promising.

Key Words: 9






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
ANN THORAC SURG ASIAN CARDIOVASC THORAC ANN EUR J CARDIOTHORAC SURG
J THORAC CARDIOVASC SURG ICVTS ALL CTSNet JOURNALS
Copyright © 2003 by The American Association for Thoracic Surgery.