Oxygen free radicals in cardiac transplantation

After prolonged ischemia, reperfusion of the myocardium with oxygenated blood results in high levels of superoxide anions. Several mechanisms for superoxide anion generation have been proposed, including increased xanthine oxidase activity, neutrophil activation, and arachidonate cascade activation. Superoxide anion accumulation may cause enzyme inactivation and lipid peroxidation in the sarcolemma with resultant intracellular calcium accumulation and excitation-contraction uncoupling. A review of a number of animal studies has shown that free radical scavengers such as superoxide dismutase and catalase can preserve myocardial function and metabolism during transplantation. In addition, other data indicate a role for inhibitors of free radical generation (i.e., allopurinol or oxypurinol), iron chelators (i.e., deferoxamine), or metabolic substrates such as L-glutamate in the inhibition of free radical myocardial injury. In addition, glutathione has been demonstrated to produce faster recovery of ventricular function in hypothermia preserved and reperfused rat hearts, presumably by inhibiting free radical production. Confirmatory data for human cardiac transplantation is not yet available.