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 vascular permeability (VP) and (2) the effects of TXA or APR on platelet-activating factor (PAF)-induced increase of VP in normal unanesthetized rats. Evans blue dye (EB) bound to albumin was used as the marker of extravasation in selected tissues. In normal rats, PAF (1 microg/kg i.v.) increased VP in most selected tissues including bronchi, aorta, duodenum and pancreas without affecting blood pressure. TXA (up to 300 mg/kg i.v.) had no significant effect on basal VP in any tissues, while APR (30000 KIU/kg i.v.) decreased basal 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%. TXA was mostly effective at an i.v. dose of 100 mg/kg with a 2 h of pre-treatment period. Pre-treatment with APR also reduced PAF-induced increases of VP in selected tissues by 35 to 61%. The i.v. dose of 30000 KIU/mg was optimal when injected at least 30 min before the administration of PAF + Evans blue. These results suggest that the beneficial effect of APR and TXA, following cardiopulmonary bypass (CPB) and other type of surgeries, may be attributed to the inhibition of plasma exudation mediated, at least in part, by PAF. Thus, TXA and APR may improve patients recovery by reducing the capillary leakage of albumin, associated with interstitial edema formation, and maintaining intravascular fluid volume.
O'Brien
J G
JG
Department of Pharmacology, Faculty of Medicine, University of Sherbrooke, Canada.
Battistini
B
B
Zaharia
F
F
Plante
G E
GE
Sirois
P
P
D000818:Animals; D000933:Antifibrinolytic Agents / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects; D007611:Aprotinin / Q000494:pharmacology*; D001980:Bronchi / Q000098:blood supply; D019559:Capillary Leak Syndrome / Q000517:prevention & control*; D002199:Capillary Permeability / Q000187:drug effects*; D004396:Coloring Agents / Q000493:pharmacokinetics; D004386:Duodenum / Q000098:blood supply; D005070:Evans Blue / Q000493:pharmacokinetics; D005119:Extravasation of Diagnostic and Therapeutic Materials / Q000517:prevention & control*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D009928:Organ Specificity; D010179:Pancreas / Q000098:blood supply; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors* / Q000494:pharmacology / Q000502:physiology; D011183:Postoperative Complications / Q000517:prevention & control; D011652:Pulmonary Circulation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014148:Tranexamic Acid / Q000494:pharmacology*
D000933:Antifibrinolytic Agents; D004396:Coloring Agents; D010972:Platelet Activating Factor; D005070:Evans Blue; D014148:Tranexamic Acid; D007611:Aprotinin