Incremental iron overload during reperfusion progressively augments oxidative injury.
OBJECTIVE
To determine if a relationship exists between the extent of iron-catalyzed injury and the degree of tissue iron overload during reperfusion.


METHODS
To selectively increase tissue iron only during early reperfusion, isolated, buffer perfused rabbit hearts were exposed to 20 microM Fe(2+)-100 microM ADP during the last 3 minutes of ischemia and the initial 4 minutes of reperfusion. Control groups were exposed to ADP and iron-ADP regimens that did not increase intracellular iron. All the hearts received 30 minutes of normothermic global ischemia and 30 minutes of reperfusion. Heart function was monitored continuously throughout each experiment. Tissue iron and biochemical markers were analyzed at the end of experiments.


RESULTS
Hemodynamic recovery was decreased and tissue lipid peroxide levels were increased in the 20 microM Fe(2+)-100 microM ADP group compared to controls. The recoveries of developed pressure and positive/negative dP/dT at 30 minutes of reperfusion were negatively correlated with tissue iron levels, while cytosol and membrane lipid peroxide levels correlated positively with the iron levels during reperfusion.


CONCLUSIONS
The extent of oxidative injury during reperfusion was directly related to the tissue iron burden present during reperfusion. Increased lipid peroxidation was the principal chemical marker of iron-catalyzed injury.
Jian
Y
Y
Department of Medicine, Case Western Reserve University, Cleveland, Ohio, USA.
Lesnefsky
E J
EJ
D000818:Animals; D001794:Blood Pressure; D002462:Cell Membrane / Q000378:metabolism; D003402:Creatine Kinase / Q000378:metabolism; D066298:In Vitro Techniques; D007501:Iron / Q000378:metabolism*; D008054:Lipid Peroxides / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000503:physiopathology; D010084:Oxidation-Reduction; D011817:Rabbits
D008054:Lipid Peroxides; D007501:Iron; D003402:Creatine Kinase