Effect of tissue-plasminogen activator on leukocyte-endothelial interactions at the microcirculatory level

In free tissue transfer and replantation surgery, there is a debate over wh ether any pharmacologic agents should be used to improve vessel patency and tissue survival. Because tissue-plasminogen activator (t-PA) is a highly e ffective and safe fibrinolytic, it may be useful in obtaining and maintaini ng vessel patency. The direct effects of t-PA on skeletal muscle hemodynami cs and leukocyte activa tion at the microcirculatory level were investigate d. Male Sprague-Dawley rats (n = 20) were divided into three experimental g roups: control(n = 8),vehicle (n = 6),and t-PA (n = 6). Using the cremaster muscle flap model and intravital microscopy, red blood cell velocity, vess el diameter, capillary perfusion, endothelial edema index, and leukocyte-en dothelial interactions (rolling, adhering, and transmigrating leukocytes) i n postcapillary venules were measured. In the vehicle and t-PA groups, vehi cle or t-PA was infused by means of a catheter inserted into the lower abdo minal aorta for local infusion. Except for a significant reduction in the d iameter of the first order arterioles from 117 mu m to 82 mu m (medians; p = 0.026), t-PA did not significantly affect red blood cell velocity, vessel diameter, or capillary perfusion compared with vehicle. However, leukocyte -endothelial interactions did differ significantly in postcapillary venules . Adhering leukocytes counted per visual field decreased from 4.67 in the v ehicle group and 3.50 in the control group to 1.67 in the t-PA group (media ns; p = 0.015 and p = 0.005, respectively); transmigrating leukocytes in th e t-PA group decreased from 4.75 in the vehicle group and 3.50 in the contr ol group to 1.61 in the t-PA group (medians; p = 0.002 and p = 0.043, respe ctively), t-PA treatment significantly decreased the number of both adherin g and transmigrating leukocytes. These novel findings on leukocyte-endothel ial interactions suggest that t-PA has anti-inflammatory effect.