TY - JOUR
T1 - Impact of 24 h continuous hypothermic perfusion on heart preservation by assessment of oxidative stress
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.
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2004
Y1 - 2004
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.
AB - 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.
KW - Heart transplant
KW - Hypothermic perfusion
KW - Organ preservation
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U2 - 10.1111/j.1399-0012.2004.00213
DO - 10.1111/j.1399-0012.2004.00213
M3 - Article
C2 - 15217403
AN - SCOPUS:4544327235
SN - 1399-6738
VL - 18
SP - 22
EP - 27
JO - Clinical Transplantation, Supplement
JF - Clinical Transplantation, Supplement
IS - 12
ER -