Twenty-four-hour heart preservation using continuous cold perfusion and copper (II) complexes

Background. During long-term in vitro heart preservation and subsequent rep erfusion, irreversible tissue damage occurs in part due to reactive oxygen species. Therefore, inhibition of generation of oxygen-derived free radical s and the related oxidative damage of ischemic tissue may be useful in main taining heart function after long-term preservation, Complexes of Cu(II) ma y cause disproportionation of superoxide and thus may function as an inhibi tor of the effects of oxygen-derived free radicals. Methods. In this study, 24-h preservation of isolated rat hearts was perfor med. Using the Langendorff technique, hearts were perfused for 24 h with a hypothermic, moderately hyperkalemic (15 mM KCl) solution containing variou s metabolic and membrane-stabilizing additives at constant low pressure. In addition, the potential benefit of the addition of two Cu(II) compounds (C u(II) Cl-2 and Cu(II)(2)Asp(2)) to the perfusion solution was examined, Results. The Cu(II)Cl-2-treated hearts were significantly better preserved than control hearts after 24 h of preservation with regard to recovery of s ystolic pressure, coronary flow, max +dP/dt, and max -dP/dt. Lipid peroxida tion as estimated by myocardial malonaldehyde (both P < 0.001) and myocardi al creatine kinase release (both P < 0.05 vs control) were significantly re duced in the Cu(II)Cl-2 and Cu(II)(2)Asp(4) groups. Overall, Cu(II)Cl-2 bes t preserved the heart after 24 h of cold preservation with respect to indic es of functional recovery, whereas Cu(II)(2)Asp(4) did not significantly im prove functional recovery compared to control. Conclusion. Low-pressure, cold perfusion with an enhanced solution is a pot ential method to preserve donor hearts in preparation for transplantation. The beneficial effect of Cu(II)Cl-2 was attributed to (i) SOD activity of t he Cu2+ species and/or (ii) termination of chain carriers in the lipid pero xidations by aqueous Cu2+ and Cu+ species. The negation of some of the posi tive effects of Cu2+ species by the introduction of acetylsalicylate was te ntaively assigned to potentiation of the Ca2+ modality for reperfusion inju ry. (C) 1998 Academic Press.