Reperfusion of ischemic tissues can be associated with structural and functional injury, which is referred to as
ischemia-reperfusion injury.
Superoxide dismutase is an endogenous
free radical scavenger that converts toxic
oxygen derived
free radicals to
hydrogen peroxide. With the development of gene cloning technology, the potential of manipulating cells to overexpress endogenous
proteins has been realized. Transgenic mice capable of overexpressing
superoxide dismutase, and knockout mice in which the gene responsible for its production has been deleted, were used as a model to examine the protective effects of
superoxide dismutase against
ischemia-reperfusion injury. Epigastric
island flaps were elevated in wild-type (control), transgenic
superoxide dismutase 1, and knockout
superoxide dismutase 1 mice and subjected to ischemic intervals of 0, 3, 6, 9, or 12 hours. Five animals were studied at each time point in each study group. Flap viability was assessed on postoperative day 7. Baseline wild-type flap survival was 100 percent after 3 hours of
ischemia and subsequent reperfusion; survival decreased to 21 percent after 9 hours of
ischemia. Transgenic mice had significantly higher flap survival than wild-type animals after 6 hours of
ischemia and subsequent reperfusion (97.0 versus 85.2 percent) and after 9 hours of
ischemia (82 versus 21 percent, p < 0.01). In knockout mice, there was complete flap
necrosis after as little as 3 hours of
ischemia. This study confirms the protective effects of
superoxide dismutase against
ischemia-reperfusion injury. In addition, its deficiency results in a dramatic susceptibility to ischemic injury.