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 oxidative injury. Isolated rat hearts were subjected to 20 min of normothermic global ischemia, followed by 30 min of reperfusion; after 20 min of preischemic loading with Krebs-Henseleit buffer +/- 20 or 30 microM zinc-bis-histidinate (Zn-His2), 0.5 mM deferoxamine (DEF) or 42 microM neocuproine (NEO). Postischemic developed systolic pressure and rate-pressure product were highest and postischemic end-diastolic pressure was lowest in hearts treated with 20 or 30 microM Zn-His2 and 0.5 mM DEF. Cu efflux was significantly increased by 225 and 290% (end of preischemic loading), and 325 and 375% (immediate postischemic period) of control basal rates in hearts treated with 30 microM Zn-His2 and 0.5 mM DEF, respectively. NEO did not effect any of these parameters. By the end of ischemia, protein carbonyls were lowest in Zn-His2-treated hearts and highest in DEF-treated hearts when compared with control hearts. The results of this study suggest that removal of redox-active Cu before ischemia has beneficial effects, indicating a mediatory role in postischemic cardiac oxidative injury.
Powell
S R
SR
Department of Obstetrics/Gynecology, Winthrop University Hospital, Mineola, New York 11501, USA. spowell@winthrop.org
Gurzenda
E M
EM
Wingertzahn
M A
MA
Wapnir
R A
RA
D000818:Animals; D000931:Antidotes / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D003300:Copper / Q000378:metabolism*; D003676:Deferoxamine / Q000494:pharmacology; D006639:Histidine / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000378:metabolism; D009942:Organometallic Compounds / Q000494:pharmacology; D018384:Oxidative Stress; D010618:Phenanthrolines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000931:Antidotes; D002614:Chelating Agents; D009942:Organometallic Compounds; D010618:Phenanthrolines; C088059:zinc bis(histidinate); D006639:Histidine; D003300:Copper; C002701:neocuproine; D003676:Deferoxamine