Twenty-Four-Hour Heart Preservation Using Continuous Cold Perfusion and Copper (II) Complexes

• Published in: The Journal of surgical research 1998-12, Vol.80 (2), p.171-176
• Main Authors: Sellke, Frank W., Wilkinson Richter, Helen, Dunphy, Gail, Azodi, Masoud, Ely, Daniel L.
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants; Aspirin - analogs & derivatives; Biological and medical sciences; Cold Temperature; Copper; Creatine Kinase - metabolism; Heart - physiology; heart preservation; heart transplantation; In Vitro Techniques; Lipid Peroxidation; Malondialdehyde - metabolism; Medical sciences; Myocardial Reperfusion Injury - metabolism; Myocardial Reperfusion Injury - prevention & control; Organ Preservation - methods; oxygen-derived free radicals; Perfusion; Rats; Rats, Inbred SHR; Reactive Oxygen Species - metabolism; reperfusion injury; scavengers; Solutions; Superoxide Dismutase - metabolism; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the heart; Time Factors; Ventricular Function, Left
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1006/jsre.1998.5457

Background.During long-termin vitroheart 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) Cl2and 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 (bothP< 0.001) and myocardial creatine kinase release (bothP< 0.05 vs control) were significantly reduced in the Cu(II)Cl2and Cu(II)2Asp4groups. Overall, Cu(II)Cl2best preserved the heart after 24 h of cold preservation with respect to indices of functional recovery, whereas Cu(II)2Asp4did 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)Cl2was 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 tentaively assigned to potentiation of the Ca2+modality for reperfusion injury.