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Twenty-four-hour heart preservation using continuous cold perfusion and copper (II) complexes
F W Sellke1, H W Richter, G Dunphy
1Department of Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, 02215, USA.
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.
Conclusion:
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.