Lipid peroxidation-derived free radical production and postischemic myocardial reperfusion injury.

ESR spin trapping techniques, which monitor LPO-derived secondary free radical production, provide a quantitative index of irreversible oxidative injury in in vivo and in vitro models of postischemic stress. Secondary radical detection, in conjunction with other indices of injury, also offers a powerful approach for assessing protection against reperfusion-mediated oxidative injury in the presence of anti-radical intervention (Fig. 11). Monitoring secondary radical production has allowed us to demonstrate (1) a direct relationship between ischemic duration and the subsequent postischemic production of alkoxyl radicals from heart tissue; (2) changes in total secondary radical levels directly parallel the severity of mechanical dysfunction and/or tissue injury in postischemic tissue models; (3) interventions that interrupt LPO-derived secondary radical production by different mechanisms also attenuate reperfusion-mediated functional and/or tissue injury; and (4) secondary radical detection provides a standard measure of injury independent of the oxidative stress model used (A-R cells; buffer- and blood-perfused tissues; and global or regional ischemia) or animal species employed (rat, hamster, swine, dog, and human models). The lack of species-specificity for this index suggests the potential for clinical application, especially in light of our recent report demonstrating detection of secondary alkoxyl and alkyl radicals during the postoperative period after human open heart surgery.