Impact of 24 h continuous hypothermic perfusion on heart preservation by assessment of oxidative stress

Torin P. Fitton, Chiming Wei, Ruxian Lin, Brian T. Bethea, Christopher J. Barreiro, Luciano Amado, Fred Gage, Joshua Hare, William A. Baumgartner, John V. Conte

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Introduction: Despite investigating numerous solutions, additives, and techniques over the last two decades, extending donor heart preservation beyond 4-6 h has not been achieved. Hypothermic heart preservation (HP) induces oxidative stress (OS) with reactive oxygen species (ROS) production, causing DNA cleavage and impairing repair. Quantification of cardiomyocyte concentrations of DNA damage by-products (8-oxoG) and mismatch repair enzymes (MYH, OGG-1, MSH2) reflects the severity of OS. If increased repair enzyme production is insufficient to repair injury, cell death occurs and functional outcomes are impacted. We investigated continuous hypothermic perfusion (CHP), a new form of HP, and the mechanism of injury associated with hypothermic storage, by assessing functional outcome and OS after allotransplantation of canine hearts. Methods: Fourteen canine hearts were harvested using standard techniques after baseline echocardiograms and haemodynamic parameters were obtained. The hearts were implanted after 24 h CHP (n = 10) or 4 h static preservation (SP; n = 4). After weaning from cardiopulmonary bypass (CPB), recipients were kept alive for 6 h. Repeat echocardiograms and haemodynamic parameters were obtained. Quantification of MYH, OGG-1, and MSH2 concentrations were performed on biopsies using immunohistochemistry and Western blot analysis. Results: Twelve out of 14 hearts (8/10 CHP; 4/4 SP) were successfully weaned on moderate inotropic support. Post-implant echocardiogram, completed in 6/10 CHP and 2/4 SP hearts, demonstrated hyperdynamic function and normal wall motion. The expression and activity of DNA repair enzymes was identical between normal baseline and CHP hearts. Conclusion: CHP reduces OS associated with prolonged hypothermic preservation and may allow longer preservation periods without compromising function. CHP offers several potential advantages: (1) resuscitation of non-beating heart donor organs, (2) time for HLA tissue typing, (3) facilitate interventions improving graft function, and (4) increased organ sharing.

Original languageEnglish (US)
Pages (from-to)22-27
Number of pages6
JournalClinical Transplantation, Supplement
Volume18
Issue number12
StatePublished - Sep 23 2004

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Oxidative Stress
Perfusion
Histocompatibility Testing
Canidae
Hemodynamics
DNA Repair Enzymes
DNA Cleavage
DNA Mismatch Repair
Wounds and Injuries
Enzymes
Cardiopulmonary Bypass
Cardiac Myocytes
Resuscitation
DNA Damage
Reactive Oxygen Species
Cell Death
Western Blotting
Immunohistochemistry
Tissue Donors
Transplants

All Science Journal Classification (ASJC) codes

  • Immunology
  • Transplantation

Cite this

Fitton, Torin P. ; Wei, Chiming ; Lin, Ruxian ; Bethea, Brian T. ; Barreiro, Christopher J. ; Amado, Luciano ; Gage, Fred ; Hare, Joshua ; Baumgartner, William A. ; Conte, John V. / Impact of 24 h continuous hypothermic perfusion on heart preservation by assessment of oxidative stress. In: Clinical Transplantation, Supplement. 2004 ; Vol. 18, No. 12. pp. 22-27.
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Fitton, TP, Wei, C, Lin, R, Bethea, BT, Barreiro, CJ, Amado, L, Gage, F, Hare, J, Baumgartner, WA & Conte, JV 2004, 'Impact of 24 h continuous hypothermic perfusion on heart preservation by assessment of oxidative stress', Clinical Transplantation, Supplement, vol. 18, no. 12, pp. 22-27.

Impact of 24 h continuous hypothermic perfusion on heart preservation by assessment of oxidative stress. / Fitton, Torin P.; Wei, Chiming; Lin, Ruxian; Bethea, Brian T.; Barreiro, Christopher J.; Amado, Luciano; Gage, Fred; Hare, Joshua; Baumgartner, William A.; Conte, John V.

In: Clinical Transplantation, Supplement, Vol. 18, No. 12, 23.09.2004, p. 22-27.

Research output: Contribution to journalArticle

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AU - Fitton, Torin P.

AU - Wei, Chiming

AU - Lin, Ruxian

AU - Bethea, Brian T.

AU - Barreiro, Christopher J.

AU - Amado, Luciano

AU - Gage, Fred

AU - Hare, Joshua

AU - Baumgartner, William A.

AU - Conte, John V.

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N2 - Introduction: Despite investigating numerous solutions, additives, and techniques over the last two decades, extending donor heart preservation beyond 4-6 h has not been achieved. Hypothermic heart preservation (HP) induces oxidative stress (OS) with reactive oxygen species (ROS) production, causing DNA cleavage and impairing repair. Quantification of cardiomyocyte concentrations of DNA damage by-products (8-oxoG) and mismatch repair enzymes (MYH, OGG-1, MSH2) reflects the severity of OS. If increased repair enzyme production is insufficient to repair injury, cell death occurs and functional outcomes are impacted. We investigated continuous hypothermic perfusion (CHP), a new form of HP, and the mechanism of injury associated with hypothermic storage, by assessing functional outcome and OS after allotransplantation of canine hearts. Methods: Fourteen canine hearts were harvested using standard techniques after baseline echocardiograms and haemodynamic parameters were obtained. The hearts were implanted after 24 h CHP (n = 10) or 4 h static preservation (SP; n = 4). After weaning from cardiopulmonary bypass (CPB), recipients were kept alive for 6 h. Repeat echocardiograms and haemodynamic parameters were obtained. Quantification of MYH, OGG-1, and MSH2 concentrations were performed on biopsies using immunohistochemistry and Western blot analysis. Results: Twelve out of 14 hearts (8/10 CHP; 4/4 SP) were successfully weaned on moderate inotropic support. Post-implant echocardiogram, completed in 6/10 CHP and 2/4 SP hearts, demonstrated hyperdynamic function and normal wall motion. The expression and activity of DNA repair enzymes was identical between normal baseline and CHP hearts. Conclusion: CHP reduces OS associated with prolonged hypothermic preservation and may allow longer preservation periods without compromising function. CHP offers several potential advantages: (1) resuscitation of non-beating heart donor organs, (2) time for HLA tissue typing, (3) facilitate interventions improving graft function, and (4) increased organ sharing.

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Fitton TP, Wei C, Lin R, Bethea BT, Barreiro CJ, Amado L et al. Impact of 24 h continuous hypothermic perfusion on heart preservation by assessment of oxidative stress. Clinical Transplantation, Supplement. 2004 Sep 23;18(12):22-27.