Aprotinin

Aprotinin is a bovine pancreatic trypsin inhibitor (BPTI) inhibitor which inhibits trypsin and chymotrypsin with K_is of 0.06 pM and 9 nM, respectively. IC50 & Target:Ki: 0.06 pM (Trypsin), 9 nM (Chymotrypsin)^[1] In Vitro: Aprotinin, a serine protease inhibitor isolated from bovine lung, is a complex protease inhibitor that is an antifibrinolytic, inhibits contact activation, and decreases the inflammatory response to cardiopulmonary bypass^[2]. Aprotinin inhibits trypsin (bovine, K_i= 0.06 pM), chymotrypsin (bovine, K_i= 9 nM), plasmin (human, 0.23 nM)^[1]. Aprotinin is also a competitive protein inhibitor of NOS activity. It inhibits NOS-I and NOS-II with K_i values of 50 μM and 78 μM, respectively^[3]. Aprotinin significantly inhibits fibrinolysis with an IC₅₀ of 0.16±0.05 μM^[4]. In Vivo: High dose aprotinin can reduce blood loss and transfusion requirements associated with primary cardiac procedures such as coronary artery bypass graft (CABG) or heart valve replacement surgery^[5]. Aprotinin inhibits thrombus formation in a dose-dependent manner. Aprotinin at a dose of 1.5 mg kg^-1 (bolus) and 3 mg kg^-1 h^-1 infusion (maintenance infusion) causes a tendency towards a reduction in bleeding time. Aprotinin significantly reduces the bleeding time starting at a dose of 3 mg kg^-1 bolus plus 6 mg kg^-1 h^-1 showing a reduction of approximately 84%±2.9%. At the highest dose of 5 mg kg^-1 and 10 mg kg^-1 h^-1, the strongest effects are observed^[4]. Aprotinin may affect tumor necrosis factor-alpha (TNF) levels. Soluble TNFRI levels are significantly increased following I/R in the aprotinin treated wild type mice and not detected in all TNFRInull mice^[6].