title: Impact of 24 h continuous hypothermic perfusion on heart preservation by assessment of oxidative stress.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: The Johns Hopkins Medical Institution, Baltimore, MD, USA.
authors.forename: Torin P
authors.initials: TP
authors.lastname: Fitton
authors.forename: Chiming
authors.initials: C
authors.lastname: Wei
authors.forename: Ruxian
authors.initials: R
authors.lastname: Lin
authors.forename: Brian T
authors.initials: BT
authors.lastname: Bethea
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Barreiro
authors.forename: Luciano
authors.initials: L
authors.lastname: Amado
authors.forename: Fred
authors.initials: F
authors.lastname: Gage
authors.forename: Joshua
authors.initials: J
authors.lastname: Hare
authors.forename: William A
authors.initials: WA
authors.lastname: Baumgartner
authors.forename: John V
authors.initials: JV
authors.lastname: Conte
mesh_terms: D000818:Animals; D004249:DNA Damage; D004285:Dogs; D006151:Guanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D016027:Heart Transplantation / Q000502:physiology; D007036:Hypothermia, Induced; D007150:Immunohistochemistry; D009926:Organ Preservation; D018384:Oxidative Stress / Q000502:physiology; D014184:Transplantation, Homologous
chemical_list: D006151:Guanosine; C046215:8-hydroxyguanosine