title: A whole blood-based perfusate provides superior preservation of myocardial function during ex vivo heart perfusion.
abstract: BACKGROUND
  Ex vivo heart perfusion (EVHP) provides the opportunity to resuscitate unused donor organs and facilitates assessments of myocardial function that are required to demonstrate organ viability before transplantation. We sought to evaluate the effect of different oxygen carriers on the preservation of myocardial function during EVHP.
  
  
  METHODS
  Twenty-seven pig hearts were perfused ex vivo in a normothermic beating state for 6 hours and transitioned into working mode for assessments after 1 (T1), 3 (T3), and 5 (T5) hours. Hearts were allocated to 4 groups according to the perfusate composition. Red blood cell concentrate (RBC, n = 6), whole blood (RBC+Plasma, n = 6), an acellular hemoglobin-based oxygen carrier (HBOC, n = 8), or HBOC plus plasma (HBOC+Plasma, n = 7) were added to STEEN Solution (XVIVO Perfusion, Goteborg, Sweden) to achieve a perfusate hemoglobin concentration of 40 g/liter.
  
  
  RESULTS
  The perfusate composition affected the preservation of systolic (T5 dP/dtmax: RBC+Plasma = 903 ± 99, RBC = 771 ± 77, HBOC+Plasma = 691 ± 82, HBOC = 563 ± 52 mm Hg/sec; p = 0.047) and diastolic (T5 dP/dtmin: RBC+Plasma = -574 ± 48, RBC = -492 ± 63, HBOC+Plasma = -326 ± 32, HBOC = -268 ± 22 mm Hg/sec; p < 0.001) function, and the development of myocardial edema (weight gain: RBC+Plasma = 6.6 ± 0.9, RBC = 6.6 ± 1.2, HBOC+Plasma = 9.8 ± 1.7, HBOC = 16.3 ± 1.9 g/hour; p < 0.001) during EVHP. RBC+Plasma hearts exhibited less histologic evidence of myocyte damage (injury score: RBC+Plasma = 0.0 ± 0.0, RBC = 0.8 ± 0.3, HBOC+Plasma = 2.6 ± 0.2, HBOC = 1.75 ± 0.4; p < 0.001) and less troponin-I release (troponin-I fold-change T1-T5: RBC+Plasma = 7.0 ± 1.7, RBC = 13.1 ± 1.6, HBOC+Plasma = 20.5 ± 1.1, HBOC = 16.7 ± 5.8; p < 0.001). Oxidative stress was minimized by the addition of plasma to RBC and HBOC hearts (oxidized phosphatidylcholine compound fold-change T1-T5: RBC+Plasma = 1.83 ± 0.20 vs RBC = 2.31 ± 0.20, p < 0.001; HBOC+Plasma = 1.23 ± 0.17 vs HBOC = 2.80 ± 0.28, p < 0.001).
  
  
  CONCLUSIONS
  A whole blood-based perfusate (RBC+Plasma) minimizes injury and provides superior preservation of myocardial function during EVHP. The beneficial effect of plasma on the preservation of myocardial function requires further investigation.
authors.affiliation: Cardiac Sciences Program, University of Manitoba, University of Manitoba, Winnipeg, Manitoba, Canada; Institute of Cardiovascular Sciences, St. Boniface Hospital, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Christopher W
authors.initials: CW
authors.lastname: White
authors.affiliation: Institute of Cardiovascular Sciences, St. Boniface Hospital, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Devin
authors.initials: D
authors.lastname: Hasanally
authors.affiliation: Cardiac Sciences Program, University of Manitoba, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Paul
authors.initials: P
authors.lastname: Mundt
authors.affiliation: Institute of Cardiovascular Sciences, St. Boniface Hospital, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Yun
authors.initials: Y
authors.lastname: Li
authors.affiliation: National Research Council Institute for Biodiagnostics, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Bo
authors.initials: B
authors.lastname: Xiang
authors.affiliation: Department of Pathology, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Julianne
authors.initials: J
authors.lastname: Klein
authors.affiliation: Institute of Cardiovascular Sciences, St. Boniface Hospital, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Alison
authors.initials: A
authors.lastname: Müller
authors.affiliation: Institute of Cardiovascular Sciences, St. Boniface Hospital, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Emma
authors.initials: E
authors.lastname: Ambrose
authors.affiliation: Cardiac Sciences Program, University of Manitoba, University of Manitoba, Winnipeg, Manitoba, Canada; Institute of Cardiovascular Sciences, St. Boniface Hospital, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Amir
authors.initials: A
authors.lastname: Ravandi
authors.affiliation: Cardiac Sciences Program, University of Manitoba, University of Manitoba, Winnipeg, Manitoba, Canada; Institute of Cardiovascular Sciences, St. Boniface Hospital, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Rakesh C
authors.initials: RC
authors.lastname: Arora
authors.affiliation: Department of Anesthesia and Perioperative Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Trevor W
authors.initials: TW
authors.lastname: Lee
authors.affiliation: Institute of Cardiovascular Sciences, St. Boniface Hospital, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Larry V
authors.initials: LV
authors.lastname: Hryshko
authors.affiliation: Papworth Hospital, Cambridge, United Kingdom.
authors.forename: Stephen
authors.initials: S
authors.lastname: Large
authors.affiliation: National Research Council Institute for Biodiagnostics, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Ganghong
authors.initials: G
authors.lastname: Tian
authors.affiliation: Cardiac Sciences Program, University of Manitoba, University of Manitoba, Winnipeg, Manitoba, Canada; Institute of Cardiovascular Sciences, St. Boniface Hospital, University of Manitoba, Winnipeg, Manitoba, Canada; Cardiac Surgery, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada; Alberta Transplant Institute, University of Alberta, Edmonton, Alberta, Canada. Electronic address: dhfreed@ualberta.ca.
authors.forename: Darren H
authors.initials: DH
authors.lastname: Freed
mesh_terms: D000818:Animals; D003971:Diastole; D004195:Disease Models, Animal; D004912:Erythrocytes; D005112:Extracorporeal Circulation; D005260:Female; D006333:Heart Failure / Q000601:surgery; D016027:Heart Transplantation; D006352:Heart Ventricles / Q000187:drug effects*; D009206:Myocardium; D019188:Organ Preservation Solutions / Q000494:pharmacology*; D010477:Perfusion / Q000379:methods*; D013552:Swine; D013599:Systole; D016277:Ventricular Function, Left / Q000187:drug effects*
chemical_list: D019188:Organ Preservation Solutions
keywords: HBOC; ex vivo heart perfusion; ex vivo perfusate; hemoglobin-based oxygen carrier; myocardial energy metabolism; myocardial function; oxygen delivery