title: HEMO2life as a protective additive to Celsior solution for static storage of donor hearts prior to transplantation.
abstract: BACKGROUND
  Prior to heart transplantation, static storage of donor hearts is currently limited to 4-5 h, despite profound hypothermia (4-8 °C). Because heart transplantation is an emergency procedure, improved protection to extend safe storage duration would be advantageous. We investigated whether the naturally respiratory pigment HEMO2life®, which is effective at hypothermia for the passive release of oxygen via oxygen gradient, could improve long-term preservation.
  
  
  METHODS
  Isolated Langendorff-perfused rat hearts (n = 12/group) were equilibrated (20 min) and function (left ventricular developed pressure: LVDP) measured by intraventricular balloon before arrest with cold (7.5 °C) Celsior®solution, either alone (control) or with the addition of HEMO2life®(Hemarina SA, Morlaix, France) at 1 g/L. Cold storage lasted 8 h prior to reperfusion (60 min) and recovery (as % of pre-ischemic function) was assessed. Hearts (minced and homogenized) were also assessed by TTC staining as a measure of viability and two hearts from each group were sliced and assessed by TTC staining for infarct size. Values are expressed as mean ± standard error of mean and analyzed by Student's t-test.
  
  
  RESULTS
  Hearts recovered rapidly in both groups to a plateau by 20 min of reperfusion; control and HEMO2life®final recovery (60 min) was 45 ± 2% and 57 ± 1% (P < 0.05) respectively. Left ventricular end-diastolic pressure recovered to a similar extent in both groups (between 31 to 35 mmHg), as did heart rate (final recovery between 84 to 89% pre-ischemic value); however, coronary flow was significantly (P < 0.05) higher in HEMO2life®group (7.5 ± 0.7 ml/min) compared to control (5.4 ± 0.4 ml/min). Viability and infarct size measurements were similar between groups.
  
  
  CONCLUSIONS
  The addition of the natural oxygen releasing pigment HEMO2life®to Celsior®preservation solution significantly improved post-ischemic recovery of heart function. This additive may have major therapeutic potential for clinical heart transplantation.
authors.affiliation: a Cardiac Surgical Research/Cardiothoracic Surgery , the Rayne Institute (King's College London), Guy's and St Thomas' NHS Foundation Trust, St Thomas' Hospital , London , UK.
authors.forename: Elaine S
authors.initials: ES
authors.lastname: Teh
authors.affiliation: b Biotechnopôle , Hemarina SA, Aéropôle Centre , Morlaix , France.
authors.forename: Franck
authors.initials: F
authors.lastname: Zal
authors.affiliation: b Biotechnopôle , Hemarina SA, Aéropôle Centre , Morlaix , France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Polard
authors.affiliation: c Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Department of Cardiovascular Surgery , Université Paris Descartes , Sorbonne Paris Cité; INSERM U 970 , Paris , France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Menasché
authors.affiliation: a Cardiac Surgical Research/Cardiothoracic Surgery , the Rayne Institute (King's College London), Guy's and St Thomas' NHS Foundation Trust, St Thomas' Hospital , London , UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Chambers
mesh_terms: D000818:Animals; D004187:Disaccharides / Q000494:pharmacology; D004573:Electrolytes / Q000494:pharmacology; D005971:Glutamates / Q000494:pharmacology; D005978:Glutathione / Q000494:pharmacology; D006321:Heart / Q000187:drug effects* / Q000502:physiology* / Q000503:physiopathology; D016027:Heart Transplantation; D006639:Histidine / Q000494:pharmacology; D008297:Male; D008353:Mannitol / Q000494:pharmacology; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology; D011309:Preservation, Biological / Q000379:methods*; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000187:drug effects; D012996:Solutions; D013997:Time Factors; D014019:Tissue Donors; D014022:Tissue Survival / Q000187:drug effects
chemical_list: C088453:Celsior; D004187:Disaccharides; D004573:Electrolytes; D005971:Glutamates; D012996:Solutions; D008353:Mannitol; D006639:Histidine; D005978:Glutathione
keywords: Extracellular hemoglobin; heart graft preservation; langendorff model; oxygen carrier