Blocking free radical production via adenoviral gene transfer decreases cardiac ischemia-reperfusion injury

Periods of cardiac ischemia followed by reperfusion can lead to either tran sient loss of function (stunning) or permanent functional loss stemming fro m infarction, depending upon the length of the ischemic period. In either c ase the primary mediator of the injury may by oxygen-derived free radicals generated upon the reestablishment of blood flow. The heart's primary defen se against peroxide, glutathione peroxidase, is depleted during ischemia. T hus, the ischemic myocardium might derive significant protection from incre ased levels of the enzyme, catalase, which can remove hydrogen peroxide in a redox-independent manner. To test these assertions, we studied the abilit y of adenoviral gene transfer to increase intracellular antioxidant activit y via catalase expression. What we observed was that increasing catalase ac tivity in the heart was sufficient to prevent the stunning associated with 15 min of ischemia followed by reperfusion.