title: The Critical Role of Bioenergetics in Donor Cardiac Allograft Preservation.
abstract: The traditional philosophy of ex vivo organ preservation has been to limit metabolic activity by storing organs in hypothermic, static conditions. This methodology cannot provide longevity of hearts for more than 4-6 h and is thereby insufficient to expand the number of available organs. Albeit at lower rate, the breakdown of ATP still occurs during hypothermia. Furthermore, cold static preservation does not prevent the permanent damage that occurs upon reperfusion known as ischemia-reperfusion (IR) injury. This damage is caused by increased reactive oxygen species (ROS) production in combination with mitochondrial permeability transition pore (mPTP) opening, highlighting the importance of mitochondria in ischemic storage. There has recently been a major paradigm shift in the field, with emerging research supporting changes in traditional storage approaches. Novel research suggests achieving metabolic homeostasis instead of attempting to limit metabolic activity which reduces IR injury and improves graft preservation. Maintaining high ATP levels and circumventing cold organ storage would be a much more sophisticated standard for organ storage and should be the focus of future research in organ preservation. Given the link between mPTP, Ca2(+), and ROS, managing Ca2(+) influx into the mitochondria during conditioning might be the next critical step towards preventing irreversible IR injury.
authors.affiliation: Department of Surgery, Division of Cardiothoracic Surgery, University of Arizona College of Medicine, 1501 North Campbell Avenue, Room 4302, Tucson, AZ, 85724, USA.|Division of Cardiology, Thoraxcenter Erasmus University Medical Center, Rotterdam, Netherlands.
authors.forename: David A
authors.initials: DA
authors.lastname: Schipper
authors.affiliation: Department of Surgery, Division of Cardiothoracic Surgery, University of Arizona College of Medicine, 1501 North Campbell Avenue, Room 4302, Tucson, AZ, 85724, USA.
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Marsh
authors.affiliation: Department of Surgery, Division of Cardiothoracic Surgery, University of Arizona College of Medicine, 1501 North Campbell Avenue, Room 4302, Tucson, AZ, 85724, USA.|Department of Physiological Sciences, University of Arizona College of Medicine, Tucson, AZ, USA.
authors.forename: Alice S
authors.initials: AS
authors.lastname: Ferng
authors.affiliation: Division of Cardiology, Thoraxcenter Erasmus University Medical Center, Rotterdam, Netherlands.
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: Duncker
authors.affiliation: Department of Neuroscience, University Medical Center Groningen, Groningen, Netherlands.
authors.forename: Jon D
authors.initials: JD
authors.lastname: Laman
authors.affiliation: Department of Surgery, Division of Cardiothoracic Surgery, University of Arizona College of Medicine, 1501 North Campbell Avenue, Room 4302, Tucson, AZ, 85724, USA. zkhalpey@surgery.arizona.edu.|Department of Physiological Sciences, University of Arizona College of Medicine, Tucson, AZ, USA. zkhalpey@surgery.arizona.edu.|Department of Translational and Regenerative Medicine, University of Arizona College of Medicine, Tucson, AZ, USA. zkhalpey@surgery.arizona.edu.|Department of Medical Imaging, University of Arizona College of Medicine, Tucson, AZ, USA. zkhalpey@surgery.arizona.edu.|Department of Biomedical Engineering, University of Arizona College of Medicine, Tucson, AZ, USA. zkhalpey@surgery.arizona.edu.
authors.forename: Zain
authors.initials: Z
authors.lastname: Khalpey
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D064591:Allografts; D000818:Animals; D020013:Calcium Signaling; D050377:Cold Ischemia; D003080:Cold Temperature; D004734:Energy Metabolism / Q000187:drug effects; D016027:Heart Transplantation / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D008929:Mitochondria, Heart / Q000378:metabolism / Q000473:pathology; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009926:Organ Preservation / Q000009:adverse effects / Q000379:methods*; D019188:Organ Preservation Solutions / Q000627:therapeutic use; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors; D014022:Tissue Survival
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D019188:Organ Preservation Solutions; D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate
keywords: Bioenergetics; Mitochondria; Preservation; Reactive oxygen species; Transplant