Effects of tranexamic acid and aprotinin, two antifibrinolytic drugs, on PAF-induced plasma extravasation in unanesthetized rats

Two antifibrinolytic drugs, tranexamic acid (TXA), and aprotinin (APR), are currently used to improve the recovery of patients following major surgery while reducing blood loss. Their mechanisms of action have yet to be fully understood. Here, we examined (1) the effects of TXA or APR on basal vascu lar permeability (VP) and (2) the effects of TXA or APR on platelet-activat ing factor (PAF)-induced increase of VP in normal unanesthetized rats. Evan s blue dye (EB) bound to albumin was used as the marker of extravasation in selected tissues. In normal rats, PAF (1 mu g/kg i.v.) increased VP in mos t selected tissues including bronchi, aorta, duodenum and pancreas without affecting blood pressure. TXA (up to 300 mg/kg i.v.) had no significant eff ect on basal VP in any tissues, while APR (30 000 KIU/kg i.v.) decreased ba sal VP in 5 out of 8 tissues. Pre-treatment with TXA decreased PAF-induced increases of VP in the microcirculation of the thoracic and abdominal aorta , the duodenum and the pancreas, from 35% to 41%. TI;A was mostly effective at an i.v. dose of 100 mg/kg with a 2 h of pre-treatment period. Pre-treat ment with APR also reduced PAF-induced increases of VP in selected tissues by 35 to 61%. The i.v. dose of 30 000 KIU/mg was optimal when injected at l east 30 min before the administration of PAF + Evans blue. These results su ggest that the beneficial effect of APR and TXA, following cardiopulmonary bypass (CPB) and other type of surgeries, may be attributed to the inhibiti on of plasma exudation mediated, at least in part, by PAF. Thus, TXA and AP R may improve patients recovery by reducting the capillary leakage of album in, associated with interstitial edema formation, and maintaining intravasc ular fluid volume.