Copper loading of hearts increases postischemic reperfusion injury.
We studied the role of copper as a potential mediator of postischemic reperfusion injury in the isolated, perfused rat heart. Hearts were equilibrated with Krebs-Henseleit buffer for 10 minutes and then loaded with copper by way of perfusion with buffer containing 20 microM copper(II)-bis-histidial for 30 minutes. Control hearts were perfused with Krebs-Henseleit buffer alone during the loading period. Hearts than were washed with buffer for 10 minutes and subjected to 20 minutes of normothermic global ischemia followed by 30 minutes of reperfusion. Atomic absorption spectroscopy revealed a 67% increase in total copper content in loaded hearts by the end of the wash. By the end of the 30-minute period of reperfusion, control hearts demonstrated a 50-60% recovery of myocardial function as determined by peak systolic pressure, contractility, and heart rate. In contrast, copper-loaded hearts exhibited virtually no functional recovery within the 30-minute time period. Using salicylate as a probe, we determined that peak and duration of .OH formation appears to be increased in copper-loaded hearts during reperfusion. Furthermore, efflux of lactic dehydrogenase was significantly increased in copper-loaded hearts. Our results clearly demonstrate that increasing cardiac content of copper results in enhanced postischemic reperfusion injury associated with increased formation of .OH, thus suggesting an important catalytic role for this transition metal.
Powell
S R
SR
Department of Surgery, North Shore University Hospital, Manhasset, NY 11030.
Hall
D
D
Shih
A
A
D000704:Analysis of Variance; D000818:Animals; D003300:Copper / Q000032:analysis / Q000378:metabolism*; D005609:Free Radicals; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D015427:Reperfusion Injury / Q000378:metabolism* / Q000503:physiopathology; D013054:Spectrophotometry, Atomic
D005609:Free Radicals; D003300:Copper