Aprotinin (CAS No: 9087-70-1) inhibits some of the enzymes in the body that break down protein, including tendon substance. Therefore, in theory, it might be able to reverse some of the tendon damage in a chronic tendon disorder. A recent European study of patella tendonitis has been published that showed aprotinin injections had a better success rate than patients who were injected with cortisone or a placebo (in the same study). Aprotinin may also work as an irritant substance (this type of injection is called 'prolotherapy') stimulating the body to produce more healing.
Aprotinin has become widely used during open heart surgery, mainly because it helps to minimize perioperative bleeding and blood product transfusions. Aprotinin also acts by decreasing the inflammatory response generated during cardiopulmonary bypass. The mechanism through which aprotinin decreases perioperative blood loss involves preservation of platelet function. During cardiopulmonary bypass, plasmin formation is induced, which in turn activates platelets and alters platelet membrane glycoprotein Ib. Glycoprotein Ib is needed for binding of von Willebrand factor, which is essential for clotting. Aprotinin is thought to protect perioperative platelet activation by inhibiting plasmin formation. Aprotinin, however, has not been found to alter the quantity of circulating platelets, emphasizing the role of aprotinin in decreasing platelet dysfunction. Aprotinin is a polyvalent reversible inhibitor of serine proteinases. Aprotinin is manufactured from bovine lungs. It consists of 58 amino acid residues that are arranged in a single polypeptide chain. The chain is cross-linked by three disulfide bridges.
The active centres of the molecule are formed by 4 lysine groups; the tertiary structure shows a pear-shaped unit which fits exactly into the binding cavity of the serine proteinases. Due to its inner stability, the inhibitor molecule is not altered by complex formation with the enzyme.
Aprotinin is used in the treatment of haemorrhage associated with raised plasma concentrations of plasmin. It is also used to reduce blood loss and transfusion requirements in patients at high risk of major blood loss during and following open heart surgery with extra-corporeal blood circulation.
Aprotinin is a broad spectrum protease inhibitor which modulates the systemic inflammatory response (SIR) associated with cardiopulmonary bypass (CPB) surgery. SIR results in the interrelated activation of the hemostatic, fibrinolytic, cellular and humoral inflammatory systems. Aprotinin, through its inhibition of multiple mediators [e.g., kallikrein, plasmin] results in the attenuation of inflammatory responses, fibrinolysis, and thrombin generation. The effects of aprotinin use in CPB involves a reduction in inflammatory response which translates into a decreased need for allogeneic blood transfusions, reduced bleeding, and decreased mediastinal re-exploration for bleeding.