Attenuation of DNA damage in canine hearts preserved by continuous hypothermic perfusion

Torin P. Fitton, Christopher J. Barreiro, Pramod N. Bonde, Chiming Wei, Fred Gage, Rene Rodriguez, John V. Conte

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Abstract

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°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.

Original languageEnglish (US)
Pages (from-to)1812-1820
Number of pages9
JournalAnnals of Thoracic Surgery
Volume80
Issue number5
DOIs
Publication statusPublished - Nov 2005

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ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery

Cite this

Fitton, T. P., Barreiro, C. J., Bonde, P. N., Wei, C., Gage, F., Rodriguez, R., & Conte, J. V. (2005). Attenuation of DNA damage in canine hearts preserved by continuous hypothermic perfusion. Annals of Thoracic Surgery, 80(5), 1812-1820. https://doi.org/10.1016/j.athoracsur.2005.04.081