EUK-8 A SYNTHETIC CATALYTIC SCAVENGER OF REACTIVE OXYGEN SPECIES PROTECTS ISOLATED IRON-OVERLOADED RAT-HEART FROM FUNCTIONAL AND STRUCTURALDAMAGE-INDUCED BY ISCHEMIA REPERFUSION/

The effects of EUK-8, a synthetic, catalytic scavenger of reactive oxy gen species, on isolated iron-overloaded rat hearts submitted to ische mia-reperfusion were studied. In the absence of EUK-8, functional para meters (systolic and diastolic pressures, oxygen consumption as estima ted by the product heart rate times left ventricular diastolic pressur e) were severely impaired 1 minute and 15 minutes after reperfusion fo llowing a 15 minute ischemic episode. Dimethylthiourea (10 mM), a hydr oxyl radical scavenger, had a minimally protective effect. In contrast , EUK-8 at a concentration of 50 mu M in the perfusion medium maintain ed these parameters at close to their preischemia values. Electron mic roscopic analysis of heart tissues after 15 minutes ischemia followed by 15 minutes reperfusion showed extensive damage to mitochondria and sarcomeres in untreated hearts, while the extent of damage was signifi cantly lower in EUK-8-treated hearts. The functional and structural pr otection afforded by EUK-8 were significantly better than those induce d by dimethylthiourea. These data suggest that EUK-8 may be therapeuti cally useful in preventing heart damage induced by ischemia-reperfusio n, for example, during thrombolytic treatment of myocardial infarction .