Heparin Prevents Stasis-Induced Thrombosis through Protection of the Venous Endothelial Cells: An Electron Microscopic Study in Rabbits

Abstract

This study was performed to see whether or not protection of the endothelial cells contributes to the antithrombotic effects of heparin. New Zealand albino rabbits were subjected to jugular vein stasis by single caudal ligation for 2 h. Three treatments were given: saline (control group), heparin (0.2 mg/kg) 5 or 45 min before ligature of the vein. Groups of 6-8 animals were killed at 0, 5, 15, 30 and 120 min. The following parameters were determined: (1) involution and damage of the endothelial cells by scanning and transmission electron microscopy; (2) incidence and weight of thrombi in the lumens of the veins after 2 h stasis, and (3) effects of heparin on APTT and anti-Xa activity. In the control group, stasis caused a considerable involution of the endothelial cells in the first 30 min, followed by fibrin deposition and thrombus generation. Heparin strongly reduced the damage to the endothelial cells, with very evident protection of the cell membranes, and prevented thrombus generation: there were significant decreases in both incidence and weight of thrombi. These effects of heparin were evident both shortly after (maximal anticoagulant effect) and long after (no anticoagulant effect) pretreatment. We think that, under the experimental conditions we used, heparin prevented venous thrombosis at least partially by protection of the endothelial cells, through unknown mechanisms.