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 r eperfusion. Methods. To selectively increase tissue iron only during e arly reperfusion, isolated, buffer perfused rabbit hearts were exposed to 20 mu M Fe2+-100 mu M ADP during the last 3 minutes of ischemia an d the initial 4 minutes of reperfusion. Control groups were exposed to ADP and iron-ADP regimens that did not increase intracellular iron. A ll the hearts received 30 minutes of normothermic global ischemia and 30 minutes of reperfusion. Heart function was monitored continuously t hroughout each experiment. Tissue iron and biochemical markers were an alyzed at the end of experiments. Results. Hemodynamic recovery was de creased and tissue lipid peroxide levels were increased in the 20 mu M Fe2+-100 mu M ADP group compared to controls. The recoveries of devel oped 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 le vels during reperfusion. Conclusion. The extent of oxidative injury du ring reperfusion was directly related to the tissue iron burden presen t during reperfusion. Increased lipid peroxidation was the principal c hemical marker of iron-catalyzed injury.