Document Detail

Attenuation of DNA damage in canine hearts preserved by continuous hypothermic perfusion.
MedLine Citation:
PMID:  16242460     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Continuous hypothermic perfusion is a novel cardiac preservation technique. Reactive oxygen species play a role in ischemia reperfusion injury and limit organ preservation. Oxidative stress mediates a DNA mismatch lesion (7, 8-dihydro-8-oxoguanine [8-oxo-G]), which is repaired by the enzymes MutY homologue (MYH), 8-oxo-G glycosylase (OGG1), and MutS homologue 2 (MSH2). We hypothesized that continuous hypothermic perfusion would allow for maintenance of cardiac function while attenuating myocardial DNA damage with respect to the current clinical practice of static preservation at 4 degrees C. METHODS: In our canine orthotopic transplant model, donor hearts were harvested after echocardiograms, and hemodynamic studies were obtained and served as controls. The hearts were transplanted after 24 hours of continuous hypothermic perfusion or 4 hours of static preservation, and were studied for 6 hours. Quantification of 8-oxo-G lesions, MYH, OGG1, and MSH2 concentrations were performed on biopsies using immunohistochemistry. RESULTS: Postimplant echocardiograms, completed in 7 continuously perfused and 8 statically preserved hearts, demonstrated good function and normal wall motion. Positive staining for 8-oxoG was markedly increased in the static preservation group. Staining density for MYH, OGG1, and MSH2 were significantly decreased in statically preserved hearts and equivalent between continuously perfused and control hearts. CONCLUSIONS: The DNA damage assayed by 8-oxoG was significantly increased in statically preserved versus continuously perfused hearts. The DNA repair enzymes MYH, OGG1, and MSH2 were also markedly decreased in the static preservation versus continuous hypothermic perfusion groups. Continuous hypothermic perfusion reduces oxidative damage and extends preservation without compromising function.
Torin P Fitton; Christopher J Barreiro; Pramod N Bonde; Chiming Wei; Fred Gage; Rene Rodriguez; John V Conte
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Annals of thoracic surgery     Volume:  80     ISSN:  1552-6259     ISO Abbreviation:  Ann. Thorac. Surg.     Publication Date:  2005 Nov 
Date Detail:
Created Date:  2005-10-24     Completed Date:  2006-11-02     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  15030100R     Medline TA:  Ann Thorac Surg     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1812-20     Citation Subset:  AIM; IM    
Division of Cardiac Surgery, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA.
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MeSH Terms
DNA Damage
Heart Transplantation / methods*
Hypothermia, Induced / methods*
Microarray Analysis
Myocardium / enzymology
Organ Preservation / methods*

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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