Accelerated Thrombolysis In Vitro Evaluation of Agents and Methods of Administration

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Abstract
Three groups of experiments were conducted in vitro to determine (1) the relative rates of thrombolysis produced by current clinically-relevant concentrations of streptokinase (SK), urokinase (UK), tissue-type plasminogen activator (t-PA), and plasmin; (2) the concentration-response curves for each agent; and (3) the advantages of mechanical admixture of fibrinolytic agents over simple soak. For Group 1 and 2 experiments, thrombolysis was quantitated by weighing freshly prepared clots before and after 2-hour fibrinolytic soaks. For experiments in Group 3, radio-labeled fibrinogen clots were used, and the amount of lysis was determined by measuring radioactivity in residual clot and supernatant fluid. Results indicated that SK, UK, plasmin, and t-PA in saline all produced roughly equivalent rates of lysis at molarity of 10− 6. Concentrations of SK above this level (corresponding to above 5000 units/ml) slowed lysis markedly; progressively increasing concentrations of UK and t-PA produced faster lysis, with slope of about 17 and 37%, respectively, per log10 of concentration. The efficacy of fibrinolytic agents was significantly enhanced by admixing clot and agent, using intrathrombic injections or clot maceration. With clot volumes of 0.5 ml, residual clot was frequently only ½ to ⅓ as much from macerated clots as from clots that were soaked whole. With the further addition of intrathrombic plasminogen, lysis was nearly completed after 30 minutes.