Free radicals in reperfusion-induced arrhythmias: study with EUK 8, a novel nonprotein catalytic antioxidant

Oxyradicals have been implicated as a possible cause of postischemic reperfusion arrhythmias (RA). However, the ability of enzymatic scavengers such as superoxide dismutase and/or catalase to reduce RA remains controversial. The purpose of the present work was to determine whether a nonprotein catalytic antioxidant, EUK 8, may limit RA in isolated heart preparations. The catalytic dismutation of H2O2 by EUK 8 was demonstrated using a Clark electrode. EUK 8's ability to scavenge oxyradicals was studied in vitro by electron spin resonance (ESR) in presence of superoxide-anion generating system. ESR concentration-effect curves obtained led us to use EUK 8 at 50 mumol/l in isolated heart preparations. Isolated rat hearts were submitted to 10 min regional ischemia induced by left coronary artery ligation. Reperfusion was achieved by releasing the coronary ligation, and the incidence and duration of early ventricular arrhythmias were then investigated. In the treated-group, EUK 8 was added to the perfusion fluid (50 mumol/l) 90 s before reperfusion. Our results show that EUK 8 significantly reduced the severity of RA as assessed by the arrhythmia score measurement (control: 3.46 +/- 0.21 vs. EUK 8: 2.73 +/- 0.27, p < .05). In conclusion, EUK 8 is able to limit RA in our experimental model. This effect might be related to the catalytic antioxidant properties of this complex.