Iron chelation prevents tissue injury following ischemia

Abstract

Damage to a tissue following ischemia appears top occur during its reperfusion with oxygenated blood. This damage is apparently oxidative in nature and is generally considered to be the result of excessive superoxide (O₂⁻ and hydrogen peroxide (H₂O₂) production. Since neither O₂⁻ nor H₂O₂ cause oxidative damage in the absence of iron, we proposed that the oxidative processes are caused by the released of iron during reperfusion. The damage caused by the iron is exacerbated by hypoperfusion and the loss of calcium homeostasis. Our hypothesis is supported by the finding of significant levels of low molecular weight, chelatable iron in tissues during reperfusion following ischemia. The tissue damage can be ameliorated by techniques that increase the rate of reperfusion (open chest direct heart massage for the cardiac arrest model) and the administration of an iron chelator plus a calcium antagonist. Animals treated in this manner appear to completely recover from 15 minutes of cardiac arrest.