The effect of lazaroid (U74500A), a novel inhibitor of lipid peroxidation, on 24-hour heart preservation. A study based on a working model using cross-circulated blood-perfused rabbit hearts.

Lazaroid, an inhibitor of iron-mediated lipid peroxidation, has been shown to reduce free radical-mediated injury after ischemia and reperfusion. We thus examined the efficacy of pretreatment with lazaroid (U74500A) in enhancing functional recovery after 24-hr heart preservation. An isolated rabbit heart model perfused with the blood from a support rabbit was used. Before preservation, either U74500A (4 mg/kg, group L; n = 6) or solvent (group S; n = 7) was given to the donor rabbit. After 24-hr preservation with UW solution at 0 degrees C, all hearts were perfused with cross-circulated blood for 60 min with the Langendorff mode followed by 40 min of the working mode. In group S, ventricular fibrillation (Vf) after reperfusion was observed in all hearts, whereas no Vf was observed in the U74500A-pretreated group. In group L, the serum creatine phosphokinase; its isozyme, troponin-T; and serum lipid peroxide levels after 10 min of reperfusion were all significantly (P < 0.05) lower than those in group S. The Frank-Starling curve (indicating the left atrial pressure-aortic flow relationship) showed a significant left and upward shift in group L compared with that in group S (P < 0.0001). The heart pretreated with U74500A showed less ischemia-reperfusion injury, better ventricular function, and a lower lipid peroxide level. We thus conclude that the inhibition of lipid peroxidation with lazaroid appears to offer some potential benefits for long-term heart preservation.