title: Sub-normothermic preservation of donor hearts for transplantation using a novel solution, Somah: a comparative pre-clinical study.
abstract: BACKGROUND
  Hearts preserved ex vivo at extreme hypothermia (4°C) undergo time-dependent irreversible injury. Our studies using a novel solution, Somah, suggest that hearts are viably preserved at 21°C. In this study we evaluate the relative efficacy of Somah for preservation of hearts at 21°C when compared with the clinically used Celsior and University of Wisconsin (UWS) solutions.
  
  
  METHODS
  Porcine hearts arrested by cardioplegia at 21°C using Somah, Celsior or UWS solution were stored in the respective solutions at 21°C (n = 5) for 5 hours and then reperfused ex vivo for functional assessment. We assessed development of edema, cardiac tissue high-energy phosphate (HEP; ATP + creatine phosphate) levels and release of cardiac enzymes. Alterations in left ventricular wall thicknesses and functional parameters were examined by 2-dimensional (2D) echocardiography. Changes in myocardial oxygen consumption (MVO2) and lactate utilization were assessed at reperfusion.
  
  
  RESULTS
  Heart weights were unaltered during 5-hour storage in all groups. After storage, HEP levels were 28.33 ± 5.51, 10.20 ± 2.78 and 5.92 ± 1.46 nmol/liter per milligram protein (p < 0.001) in the Somah, Celsior and UWS group hearts, respectively. Upon reanimation, 2D echocardiography showed edema in the Celsior and UWS hearts; prompt attainment of physiologic function was associated with rapid establishment of aerobic metabolism not requiring stimulatory interventions in the Somah hearts, but not in the Celsior/UWS hearts. Percent fractional area change, ejection fraction and stroke volume were significantly higher (p < 0.001) in Somah hearts than in Celsior and UWS group hearts.
  
  
  CONCLUSIONS
  Increased synthesis of HEP, rapid metabolic switch and optimal function together provide evidence that hearts procured for transplantation are preserved in a superior viable condition at 21°C with Somah, but not with other commonly used clinical preservation solutions.
authors.affiliation: Division Cardiothoracic Surgery, Department of Surgery, Harvard Medical School, Boston, Massachusetts; Department of Surgery, Brigham and Women׳s Hospital, Boston, Massachusetts; VA Boston Healthcare System, Boston, Massachusetts.
authors.forename: Samar K
authors.initials: SK
authors.lastname: Lowalekar
authors.affiliation: Division Cardiothoracic Surgery, Department of Surgery, Harvard Medical School, Boston, Massachusetts; Department of Surgery, Brigham and Women׳s Hospital, Boston, Massachusetts; VA Boston Healthcare System, Boston, Massachusetts.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Cao
authors.affiliation: Division Cardiothoracic Surgery, Department of Surgery, Harvard Medical School, Boston, Massachusetts; Department of Surgery, Brigham and Women׳s Hospital, Boston, Massachusetts; VA Boston Healthcare System, Boston, Massachusetts.
authors.forename: Xiu-Gui
authors.initials: XG
authors.lastname: Lu
authors.affiliation: VA Boston Healthcare System, Boston, Massachusetts.
authors.forename: Patrick R
authors.initials: PR
authors.lastname: Treanor
authors.affiliation: Division Cardiothoracic Surgery, Department of Surgery, Harvard Medical School, Boston, Massachusetts; Department of Surgery, Brigham and Women׳s Hospital, Boston, Massachusetts; VA Boston Healthcare System, Boston, Massachusetts. Electronic address: hemant_thatte@hms.harvard.edu.
authors.forename: Hemant S
authors.initials: HS
authors.lastname: Thatte
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D002331:Carnitine / Q000494:pharmacology; D002336:Carnosine / Q000494:pharmacology; D015925:Cryopreservation / Q000379:methods*; D004187:Disaccharides / Q000494:pharmacology; D004573:Electrolytes / Q000494:pharmacology; D005260:Female; D005947:Glucose / Q000494:pharmacology; D005971:Glutamates / Q000494:pharmacology; D005978:Glutathione / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D016027:Heart Transplantation; D006639:Histidine / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007773:Lactates; D008353:Mannitol / Q000494:pharmacology; D009926:Organ Preservation / Q000379:methods*; D019188:Organ Preservation Solutions / Q000494:pharmacology*; D010101:Oxygen Consumption; D011887:Raffinose / Q000494:pharmacology; D012965:Sodium Chloride / Q000494:pharmacology; D013552:Swine; D013696:Temperature; D013997:Time Factors; D014022:Tissue Survival / Q000187:drug effects* / Q000502:physiology
chemical_list: C088453:Celsior; D004187:Disaccharides; D004573:Electrolytes; D005971:Glutamates; D007328:Insulin; D007773:Lactates; D019188:Organ Preservation Solutions; C000597593:Somah; C055206:University of Wisconsin-lactobionate solution; D008353:Mannitol; D012965:Sodium Chloride; D006639:Histidine; D000493:Allopurinol; D002336:Carnosine; D005978:Glutathione; D005947:Glucose; D000241:Adenosine; D011887:Raffinose; D002331:Carnitine
keywords: 2D echo; ex vivo cardiac function; high energy phosphates; in vitro cardiac animation; organ edema; organ preservation solutions; transplantation