Molecular Exchange between Blood and in vitro Thrombi

Abstract

Uptake of radioiodinated Lys-plasminogen (¹²⁵I-PLG), albumin (¹²⁵I-ALB), and tritiated water (³H-H₂O) by in vitro thrombi and interchange of these molecules with blood in an in vitro perfusion system were investigated. The radioisotopes were taken up by thrombi either by incorporation during formation in radiolabelled blood or by perfusion of preformed nonradioactive thrombi in radiolabelled blood. Release of the radioisotopes into a perfusion medium of nonradiolabelled blood was then monitored over a 120-min period. The small molecules of ³H-H₂O were rapidly released from the thrombi and achieved equilibrium with the perfusion medium by 120 min in that the specific radioactivity (cpm/mg) of the thrombi equalled that of the medium. The larger molecules of ¹²⁵I-PLG and ¹²⁵I-ALB were more slowly released and did not reach equilibrium with the perfusion medium over the period studied. Release of ¹²⁵I-ALB was intermediate between that of ³H-H₂O and ¹²⁵I-PLG. The greater retention of ¹²⁵I-PLG by the thrombi was consistent with the high binding affinity of plasminogen for fibrin. The demonstrated movement of these radioisotopes between medium and thrombus suggests that thrombi exist in blood in a dynamic state of flux, exhibiting a fluid exchange of molecules between the interstitial compartment of the thrombus and blood.

Kinetics of Urokinase-Induced Thrombolysis in a Biphasic in vitro System

“…It can no longer be characterized solely in terms of intrinsic or extrinsic lysis, but rather as an intricate set of interactions, involving both a liquid medium and a solid, yet perme able, thrombus that can exchange substances with the medium in which it is perfused [15]. Based on the results of the present study, it is concluded that in a blood-thrombus biphasic thrombolytic system induced by UK, there is interaction between the phases, and that PLG in both phases influences thrombolysis.…”

“…In addition, the predom inantly solid thrombus is permeable to plasma so that the liquid phase extends into the interstitial compartment of the thrombus thereby linking the interior of the thrombus with the surrounding liquid perfusion me dium. In a previous study [15] it was shown that radiolabclled plasminogen (PLG), albu min and water may diffuse into an in vitro thrombus from the surrounding plasma me dium and out again. Thus, there is, in fact, interchange of plasma constituents between the internal milieu of an in vitro thrombus and the external milieu of plasma that bathes it.…”