Diffusion Limited Delivery of Streptokinase and tPA to a Thrombus

Abstract

The delivery of the thrombolytics streptokinase and tissue plasminogen activator (tPA) from intravenous administration is studied computationally, in particular focusing on the convection, diffusion, and reaction in a fully occluded vessel. The thrombolytic was convectively transported approximately two occluded vessel diameters and was diffusively transported the remaining distance to the thrombus. The time required for complete reaction of the thrombolytic and the total amount of thrombolytic that reacts at the thrombus were found to be primarily functions of the length of the occluded vessel. The diameter and branching angle of the clogged artery are of secondary importance and the effect of flow rate along the main artery is negligible. Except for the shortest occluded vessels, intravenous delivery of the thrombolytic to the thrombus is a diffusion-limited process. Following a 1 h intravenous administration of the thrombolytic, it was found that 4–5 h are typically needed to achieve the maximum delivery of streptokinase to the thrombus; 2–3 h are needed for tPA. Less than 10−5% of the administered thrombolytic is actually delivered to the thrombus when intravenous administration is utilized. These results suggest that a drastic change in the mechanism of delivery is necessary.