Aprotinin and preservation of myocardial function after ischemia-reperfusion injury

Ischemia-reperfusion injury, a complex process involving the generation and release of inflammatory cytokines, accumulation and infiltration of neutrophils and macrophages, release of oxygen free radicals, activation of proteases, and generation of nitric oxide (NO), may result in myocardial dysfunction and possible injury to other major organs. Aprotinin, a nonspecific serine protease inhibitor used to reduce the blood loss and transfusion requirements accompanying cardiac surgery, has dose-dependent effects on coagulation, fibrinolytic, and inflammatory variables. Data indicate that aprotinin may provide protection from ischemia-reperfusion injury. In myocardial tissue models of ischemia and reperfusion, aprotinin has been shown to reduce uptake of tumor necrosis factor-alpha (TNF-alpha), generation of NO, and accumulation of leukocytes. Improved myocardial function has been observed with aprotinin treatment in animal models of ischemia-reperfusion injury. In humans, data indicate that integrin expression associated with leukocyte transmigration as well as markers of myocardial damage are reduced in patients receiving aprotinin. Further, data suggest that patients who receive aprotinin may have a reduced need for inotropic support and a decreased incidence of postoperative atrial fibrillation. In all, review of this topic indicates that aprotinin may reduce aspects of ischemia-reperfusion injury and prospective clinical studies are needed to evaluate the impact of aprotinin on associated patient outcomes.