The evaluation of plasmin and streptokinase activator complexes in a new rabbit model of venous thrombosis

Abstract

A new quantitative model for the examination of potential thrombolytic agents is described. A thrombus was formed in the inferior vena cava of the rabbit, using 125 I-labelled fibrinogen mixed with a standard amount of thromboplastin. The thrombus was anchored securely by means of a woollen thread inserted longitudinally into the lumen of the vein. Thrombotic extension of the radioactive clot and rethrombosis during the experimental period (5 h) were prevented by the administration of intravenous heparin. In control animals, the thrombus remained stable and there was no rise in te radioactivity of the circulating blood during 5 h. In animals given thrombolytic agents, lysis could be followed continuously by measuring the rise in blood radioactivity. Total lysis was determined by counting the radio-label in the residual clot after treatment. The model has been used to study the thrombolytic activity of streptokinase-human plasminogen complexes, activator-free plasmins of human and porcine origin, and human plasmin produced by streptokinase (SK) activation of human plasminogen. The role of activator complexes in the thrombolytic activity of SK-activated plasmin is discussed.