Promotion of copper excretion from the isolated rat heart attenuates postischemic cardiac oxidative injury

This study examined the role of Cu as a mediator of cardiac postischemic ox idative injury. Isolated rat hearts were subjected to 20 min of normothermi c global ischemia, followed by 30 min of reperfusion; after 20 min of preis chemic loading with Krebs-Henseleit buffer +/- 20 or 30 mu M zinc-bis-histi dinate (Zn-His(2)), 0.5 mM deferoxamine (DEF) or 42 mu M neocuproine (NEO), Postischemic developed systolic pressure and rate-pressure product were hi ghest and postischemic end-diastolic pressure was lowest in hearts treated with 20 or 30 mu M Zn-His(2) and 0.5 mM DEF. Cu efflux was significantly in creased by 225 and 290% (end of preischemic loading), and 325 and 375% (imm ediate postischemic period) of control basal rates in hearts treated with 3 0 mu M Zn-His(2) and 0.5 mM DEF, respectively. NEO did not effect any of th ese parameters. By the end of ischemia, protein carbonyls were lowest in Zn -His(2)-treated hearts and highest in DEF-treated hearts when compared with control, hearts. The results of this study suggest that removal of redox-a ctive Cu before ischemia has beneficial effects, indicating a mediatory rol e in postischemic cardiac oxidative injury.