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 r eperfusion arrhythmias (RA). However, the ability of enzymatic scaveng ers such as superoxide dismutase and/or catalase to reduce RA remains controversial. The purpose of the present work was to determine whethe r a nonprotein catalytic antioxidant, EUK 8, may limit RA in isolated heart preparations. The catalytic dismutation of H2O2 by EUK 8 was dem onstrated using a Clark electrode. EUK 8's ability to scavenge oxyradi cals was studied in vitro by electron spin resonance (ESR) in presence of superoxide-anion generating system. ESR concentration-effect curve s obtained led us to use EUK 8 at 50 mu mol/l in isolated heart prepar ations. 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 ea rly ventricular arrhythmias were then investigated. In the treated-gro up, EUK 8 was added to the perfusion fluid (50 mu mol/l) 90 s before r eperfusion. Our results show that EUK 8 significantly reduced the seve rity 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 re lated to the catalytic antioxidant properties of this complex. Copyrig ht (C) 1996 Elsevier Science Inc.