title: Twenty-four-hour heart preservation using continuous cold perfusion and copper (II) complexes.
abstract: BACKGROUND
  During long-term in vitro heart preservation and subsequent reperfusion, irreversible tissue damage occurs in part due to reactive oxygen species. Therefore, inhibition of generation of oxygen-derived free radicals and the related oxidative damage of ischemic tissue may be useful in maintaining heart function after long-term preservation. Complexes of Cu(II) may cause disproportionation of superoxide and thus may function as an inhibitor of the effects of oxygen-derived free radicals.
  
  
  METHODS
  In this study, 24-h preservation of isolated rat hearts was performed. Using the Langendorff technique, hearts were perfused for 24 h with a hypothermic, moderately hyperkalemic (15 mM KCl) solution containing various metabolic and membrane-stabilizing additives at constant low pressure. In addition, the potential benefit of the addition of two Cu(II) compounds (Cu(II) Cl2 and Cu(II)2Asp4) to the perfusion solution was examined.
  
  
  RESULTS
  The Cu(II)Cl2-treated hearts were significantly better preserved than control hearts after 24 h of preservation with regard to recovery of systolic pressure, coronary flow, max +dP/dt, and max -dP/dt. Lipid peroxidation as estimated by myocardial malonaldehyde (both P < 0. 001) and myocardial creatine kinase release (both P < 0.05 vs control) were significantly reduced in the Cu(II)Cl2 and Cu(II)2Asp4 groups. Overall, Cu(II)Cl2 best preserved the heart after 24 h of cold preservation with respect to indices of functional recovery, whereas Cu(II)2Asp4 did not significantly improve functional recovery compared to control.
  
  
  CONCLUSIONS
  Low-pressure, cold perfusion with an enhanced solution is a potential method to preserve donor hearts in preparation for transplantation. The beneficial effect of Cu(II)Cl2 was attributed to (i) SOD activity of the Cu2+ species and/or (ii) termination of chain carriers in the lipid peroxidations by aqueous Cu2+ and Cu+ species. The negation of some of the positive effects of Cu2+ species by the introduction of acetylsalicylate was tentatively assigned to potentiation of the Ca2+ modality for reperfusion injury.
authors.affiliation: Department of Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, 02215, USA.
authors.forename: F W
authors.initials: FW
authors.lastname: Sellke
authors.forename: H W
authors.initials: HW
authors.lastname: Richter
authors.forename: G
authors.initials: G
authors.lastname: Dunphy
authors.forename: M
authors.initials: M
authors.lastname: Azodi
authors.forename: D L
authors.initials: DL
authors.lastname: Ely
mesh_terms: D000818:Animals; D000975:Antioxidants; D001241:Aspirin / Q000031:analogs & derivatives; D003080:Cold Temperature; D003300:Copper; D003402:Creatine Kinase / Q000378:metabolism; D006321:Heart / Q000502:physiology; D066298:In Vitro Techniques; D015227:Lipid Peroxidation; D008315:Malondialdehyde / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control; D009926:Organ Preservation / Q000379:methods*; D010477:Perfusion; D051381:Rats; D011918:Rats, Inbred SHR; D017382:Reactive Oxygen Species / Q000378:metabolism; D012996:Solutions; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors; D016277:Ventricular Function, Left
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D012996:Solutions; C027058:tetrakis-mu-acetylsalicylato-dicopper(II); D008315:Malondialdehyde; D003300:Copper; D013482:Superoxide Dismutase; D003402:Creatine Kinase; D001241:Aspirin; C029892:cupric chloride