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 whether any pharmacologic agents should be used to improve vessel patency and tissue survival. Because tissue-plasminogen activator (t-PA) is a highly effective and safe fibrinolytic, it may be useful in obtaining and maintaining vessel patency. The direct effects of t-PA on skeletal muscle hemodynamics and leukocyte activation at the microcirculatory level were investigated. Male Sprague-Dawley rats (n = 20) were divided into three experimental groups: control (n = 8), vehicle (n = 6), and t-PA (n = 6). Using the cremaster muscle flap model and intravital microscopy, red blood cell velocity, vessel diameter, capillary perfusion, endothelial edema index, and leukocyte-endothelial interactions (rolling, adhering, and transmigrating leukocytes) in postcapillary venules were measured. In the vehicle and t-PA groups, vehicle or t-PA was infused by means of a catheter inserted into the lower abdominal aorta for local infusion. Except for a significant reduction in the diameter of the first order arterioles from 117 microm to 82 microm (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 vehicle group and 3.50 in the control group to 1.67 in the t-PA group (medians; p = 0.015 and p = 0.005, respectively); transmigrating leukocytes in the t-PA group decreased from 4.75 in the vehicle group and 3.50 in the control group to 1.67 in the t-PA group (medians; p = 0.002 and p = 0.043, respectively). t-PA treatment significantly decreased the number of both adhering and transmigrating leukocytes. These novel findings on leukocyte-endothelial interactions suggest that t-PA has anti-inflammatory effect.