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INTERACTION OF THROMBIN WITH THE VASCULAR ENDOTHELIUM IN A RECIRCULATING LANGENDORFF RABBIT HEART PREPARATION *

The vascular endothelium plays an important role in the control of hemostasis in a variety of ways, including its interaction with thrombin. The endothelial cell surface rapidly removes thrombin from the circulation in rabbits,' and appears to accelerate the thrombin-antithrombin I11 reaction.' ,z In addition, endothelial cells contain a plasma membrane protein, named thrombomodulin, which serves as a cofactor for the activation of protein C by thrombin.3-5 Kinetic studies reveal that thrombin binds thrombomodulin with high affinity on the endothelial cell surface4 but whether thrombomodulin is identical to the site(s) that clears thrombin from the circulation is uncertain. The large surface-to-volume ratio in the microcirculation makes the concentration of endothelial cell surface binding sites much higher than that observed in cultured cell monolayers and therefore would result in very different reaction rates with plasma ligands. Therefore it is desirable to have an experimental setting that approximates the in vivo situation. To study the behavior of thrombin in the microcirculation we have utilized the Langendorff heart preparation, with a plasma-free perfusate under conditions that allow quantitative assessment of thrombin binding.