Iron-load increases the susceptibility of rat hearts to oxygen reperfusion damage. Protection by the antioxidant (+)-cyanidanol-3 and deferoxamine

Abstract

To investigate whether iron is involved in the reperfusion syndrome by aggravating free radical injury, the hearts from iron-loaded and control rats were perfused under normoxic, anoxic, and reperfusion conditions. Normoxic perfusion revealed no change in coronary flow, contractility, or lactate dehydrogenase (LDH) release between these two groups. Under anoxic and reperfusion conditions, however, we found a significant increase of ventricle fibrillation (56% vs. 0%, p<0.01, n=9), a significantly lower recovery of contractility (21±7.4% vs 81±6.6%, mean ± SEM; p<0.001), and a significant increase of LDH release (667±142 vs. 268±37 mU LDH/min/g wet wt, mean ± SEM; p<0.05). Administration of either 20 μM of the antioxidant (+)-cyanidanol-3 or 50 μM of the iron-chelator deferoxamine totally prevented the generation of ventricle fibrillation and normalized contractility to control levels in the iron-loaded group. Moreover, 20 μM (+)-cyanidanol-3 significantly lowered LDH release in this period (312±67 mU), whereas deferoxamine had no protective effect on this LDH release (1,494±288 mU). Normal hearts appeared to be protected by 20 μM (+)-cyanidanol-3 as well. In this group (n=6), a significantly higher recovery of contractility (97.1±3.2% vs 81±6.6%, p<0.05) and a significantly lower release of LDH (110±27 vs. 268±37 mU, p<0.05) was found compared with the control group (n=9). No difference in superoxide dismutase or glutathione peroxidase activity was found between the groups. It is concluded that 1) iron-loaded rat hearts are more susceptible to anoxia and oxygen reperfusion damage; 2) iron load itself, under normoxic conditions, does not seem to be harmful; and 3) the antioxidant (+)-cyanidanol-3 is able to protect normal as well as iron-loaded hearts against anoxic and reperfusion damage. We suggest that iron plays an important role in the occurrence of tissue damage and ventricle fibrillation during anoxia and reperfusion, probably through the formation of hydroxyl radicals and/or perferryl oxide.