Impact of 24 h continuous hypothermic perfusion on heart preservation by assessment of oxidative stress. 2004

Torin P Fitton, and Chiming Wei, and Ruxian Lin, and Brian T Bethea, and Christopher J Barreiro, and Luciano Amado, and Fred Gage, and Joshua Hare, and William A Baumgartner, and John V Conte
The Johns Hopkins Medical Institution, Baltimore, MD, USA.

BACKGROUND Despite investigating numerous solutions, additives, and techniques over the last two decades, extending donor heart preservation beyond 4-6 h has not been achieved. Hypothermic heart preservation (HP) induces oxidative stress (OS) with reactive oxygen species (ROS) production, causing DNA cleavage and impairing repair. Quantification of cardiomyocyte concentrations of DNA damage by-products (8-oxoG) and mismatch repair enzymes (MYH, OGG-1, MSH2) reflects the severity of OS. If increased repair enzyme production is insufficient to repair injury, cell death occurs and functional outcomes are impacted. We investigated continuous hypothermic perfusion (CHP), a new form of HP, and the mechanism of injury associated with hypothermic storage, by assessing functional outcome and OS after allotransplantation of canine hearts. METHODS Fourteen canine hearts were harvested using standard techniques after baseline echocardiograms and haemodynamic parameters were obtained. The hearts were implanted after 24 h CHP (n = 10) or 4 h static preservation (SP; n = 4). After weaning from cardiopulmonary bypass (CPB), recipients were kept alive for 6 h. Repeat echocardiograms and haemodynamic parameters were obtained. Quantification of MYH, OGG-1, and MSH2 concentrations were performed on biopsies using immunohistochemistry and Western blot analysis. RESULTS Twelve out of 14 hearts (8/10 CHP; 4/4 SP) were successfully weaned on moderate inotropic support. Post-implant echocardiogram, completed in 6/10 CHP and 2/4 SP hearts, demonstrated hyperdynamic function and normal wall motion. The expression and activity of DNA repair enzymes was identical between normal baseline and CHP hearts. CONCLUSIONS CHP reduces OS associated with prolonged hypothermic preservation and may allow longer preservation periods without compromising function. CHP offers several potential advantages: (1) resuscitation of non-beating heart donor organs, (2) time for HLA tissue typing, (3) facilitate interventions improving graft function, and (4) increased organ sharing.

UI MeSH Term Description Entries
D007036 Hypothermia, Induced Abnormally low BODY TEMPERATURE that is intentionally induced in warm-blooded animals by artificial means. In humans, mild or moderate hypothermia has been used to reduce tissue damages, particularly after cardiac or spinal cord injuries and during subsequent surgeries. Induced Hypothermia,Mild Hypothermia, Induced,Moderate Hypothermia, Induced,Targeted Temperature Management,Therapeutic Hypothermia,Hypothermia, Therapeutic,Induced Mild Hypothermia,Induced Mild Hypothermias,Induced Moderate Hypothermia,Induced Moderate Hypothermias,Mild Hypothermias, Induced,Moderate Hypothermias, Induced,Targeted Temperature Managements
D007150 Immunohistochemistry Histochemical localization of immunoreactive substances using labeled antibodies as reagents. Immunocytochemistry,Immunogold Techniques,Immunogold-Silver Techniques,Immunohistocytochemistry,Immunolabeling Techniques,Immunogold Technics,Immunogold-Silver Technics,Immunolabeling Technics,Immunogold Silver Technics,Immunogold Silver Techniques,Immunogold Technic,Immunogold Technique,Immunogold-Silver Technic,Immunogold-Silver Technique,Immunolabeling Technic,Immunolabeling Technique,Technic, Immunogold,Technic, Immunogold-Silver,Technic, Immunolabeling,Technics, Immunogold,Technics, Immunogold-Silver,Technics, Immunolabeling,Technique, Immunogold,Technique, Immunogold-Silver,Technique, Immunolabeling,Techniques, Immunogold,Techniques, Immunogold-Silver,Techniques, Immunolabeling
D009926 Organ Preservation The process by which organs are kept viable outside of the organism from which they were removed (i.e., kept from decay by means of a chemical agent, cooling, or a fluid substitute that mimics the natural state within the organism). Organ Preservations,Preservation, Organ,Preservations, Organ
D004249 DNA Damage Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS. DNA Injury,DNA Lesion,DNA Lesions,Genotoxic Stress,Stress, Genotoxic,Injury, DNA,DNA Injuries
D004285 Dogs The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065) Canis familiaris,Dog
D006151 Guanosine A purine nucleoside that has guanine linked by its N9 nitrogen to the C1 carbon of ribose. It is a component of ribonucleic acid and its nucleotides play important roles in metabolism. (From Dorland, 28th ed)
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014184 Transplantation, Homologous Transplantation between individuals of the same species. Usually refers to genetically disparate individuals in contradistinction to isogeneic transplantation for genetically identical individuals. Transplantation, Allogeneic,Allogeneic Grafting,Allogeneic Transplantation,Allografting,Homografting,Homologous Transplantation,Grafting, Allogeneic
D016027 Heart Transplantation The transference of a heart from one human or animal to another. Cardiac Transplantation,Grafting, Heart,Transplantation, Cardiac,Transplantation, Heart,Cardiac Transplantations,Graftings, Heart,Heart Grafting,Heart Graftings,Heart Transplantations,Transplantations, Cardiac,Transplantations, Heart
D018384 Oxidative Stress A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). Anti-oxidative Stress,Antioxidative Stress,DNA Oxidative Damage,Nitro-Oxidative Stress,Oxidative Cleavage,Oxidative DNA Damage,Oxidative Damage,Oxidative Injury,Oxidative Nitrative Stress,Oxidative Stress Injury,Oxidative and Nitrosative Stress,Stress, Oxidative,Anti oxidative Stress,Anti-oxidative Stresses,Antioxidative Stresses,Cleavage, Oxidative,DNA Damage, Oxidative,DNA Oxidative Damages,Damage, DNA Oxidative,Damage, Oxidative,Damage, Oxidative DNA,Injury, Oxidative,Injury, Oxidative Stress,Nitrative Stress, Oxidative,Nitro Oxidative Stress,Nitro-Oxidative Stresses,Oxidative Cleavages,Oxidative DNA Damages,Oxidative Damage, DNA,Oxidative Damages,Oxidative Injuries,Oxidative Nitrative Stresses,Oxidative Stress Injuries,Oxidative Stresses,Stress Injury, Oxidative,Stress, Anti-oxidative,Stress, Antioxidative,Stress, Nitro-Oxidative,Stress, Oxidative Nitrative,Stresses, Nitro-Oxidative

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