Bradykinin receptor antagonism could reduce hyperfibrinolysis and CPB-associated blood loss. Inhibiting hyperfibrinolysis during CPB reduces blood loss and blood product requirements. On the other hand, modulating the hypofibrinolytic phase after CPB has the potential to reduce thrombotic complications. We and others have shown that bradykinin stimulates t-PA release from human forearm vasculature and the coronary circulation through a NO synthase-independent, and cyclooxygenase-independent pathway. As with vasodilation, bradykinin-stimulated t-PA release is mediated via the B2 receptor. Several groups have reported that bradykinin concentrations increase during CPB. We demonstrated a direct correlation between bradykinin and t-PA concentrations during CPB suggesting that bradykinin plays an important role in activating the fibrinolytic response during CPB. As outlined under PRELIMINARY STUDIES we have shown that HOE 140 (a B2 receptor antagonist) administered prior to CPB blunts the increase in D-dimer similar to e-aminocaproic acid. Thus, B2 receptor antagonism has the potential to reduce bradykinin-mediated fibrinolysis during CPB. In Specific Aim 2 we will test the hypothesis that bradykinin receptor antagonism modulate the fibrinolytic response observed during CPB.