title: Preservation of donor hearts using hypothermic oxygenated perfusion.
abstract: BACKGROUND
  Hypothermic machine perfusion of donor hearts enables continuous aerobic metabolism and washout of toxic metabolic byproducts. We evaluated the effect of machine perfusion on cardiac myocyte integrity in hearts preserved for 4 h in a novel device that provides pulsatile oxygenated hypothermic perfusion (Paragonix Sherpa Perfusion™ Cardiac Transport System).
  
  
  METHODS
  Pig hearts were harvested and stored in Celsior® solution for 4 h using either conventional cold storage on ice (4-h CS, n=6) or the Sherpa device (4-h pulsatile perfusion (PP), n=6). After cold preservation, hearts were evaluated using a non-working heart Langendorff system. Controls (n=3) were reperfused immediately after organ harvest. Biopsies were taken from the apex of the left ventricle before storage, after storage, and after reperfusion to measure ATP content and endothelin-1 in the tissue. Ultrastructural analysis using electron microscopy was performed.
  
  
  RESULTS
  Four-hour CS, 4-h PP, and control group did not show any significant differences in systolic or diastolic function (+dP/dt, -dP/dt, EDP). Four-hour PP hearts showed significantly more weight gain than 4-h CS after preservation, which shows that machine perfusion led to myocardial edema. Four-hour CS led to higher endothelin-1 levels after preservation, suggesting more endothelial dysfunction compared to 4-h PP. Electron microscopy revealed endothelial cell rupture and damaged muscle fibers in the 4-h CS group after reperfusion, but the cell structures were preserved in the 4-h PP group.
  
  
  CONCLUSIONS
  Hypothermic pulsatile perfusion of donor hearts leads to a better-preserved cell structure compared to the conventional cold storage method. This may lead to less risk of primary graft failure after orthotopic heart transplantation.
authors.affiliation: Department of Surgery, Transplantation Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, USA.
authors.forename: Sebastian G
authors.initials: SG
authors.lastname: Michel
authors.affiliation: Department of Surgery, Transplantation Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, USA.
authors.forename: Glenn M
authors.initials: GM
authors.lastname: La Muraglia
authors.affiliation: Department of Surgery, Transplantation Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, USA.
authors.forename: Maria Lucia L
authors.initials: ML
authors.lastname: Madariaga
authors.affiliation: Department of Surgery, Division of Cardiac Surgery, Massachusetts General Hospital, Boston, USA.
authors.forename: James S
authors.initials: JS
authors.lastname: Titus
authors.affiliation: Department of Pathology, Massachusetts General Hospital, Boston, USA.
authors.forename: Martin K
authors.initials: MK
authors.lastname: Selig
authors.affiliation: Department of Pathology, Massachusetts General Hospital, Boston, USA.
authors.forename: Evan A
authors.initials: EA
authors.lastname: Farkash
authors.affiliation: Department of Surgery, Transplantation Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, USA.
authors.forename: James S
authors.initials: JS
authors.lastname: Allan
authors.affiliation: Paragonix Technologies, Inc., Braintreee, USA.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Anderson
authors.affiliation: Department of Surgery, Transplantation Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, USA.
authors.forename: Joren C
authors.initials: JC
authors.lastname: Madsen
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003080:Cold Temperature; D004187:Disaccharides; D004573:Electrolytes; D019332:Endothelin-1 / Q000378:metabolism; D005971:Glutamates; D005978:Glutathione; D006321:Heart / Q000502:physiology; D016027:Heart Transplantation; D006639:Histidine; D008353:Mannitol; D046529:Microscopy, Electron, Transmission; D032383:Myocytes, Cardiac / Q000166:cytology / Q000502:physiology; D009926:Organ Preservation / Q000295:instrumentation* / Q000379:methods*; D019188:Organ Preservation Solutions; D010100:Oxygen; D010477:Perfusion; D011673:Pulsatile Flow; D034421:Sus scrofa; D014019:Tissue Donors; D016277:Ventricular Function, Left
chemical_list: C088453:Celsior; D004187:Disaccharides; D004573:Electrolytes; D019332:Endothelin-1; D005971:Glutamates; D019188:Organ Preservation Solutions; D008353:Mannitol; D006639:Histidine; D000255:Adenosine Triphosphate; D005978:Glutathione; D010100:Oxygen