Plasminogen-enriched pulse-spray thrombolysis with tPA: Further developments

PURPOSE: To further improve methods for pulsed plasminogen-enriched thrombo lysis and to compare results with the best obtainable with use of tissue pl asminogen activator (tPA) alone. MATERIALS AND METHODS: Parameters of plasminogen-enriched pulse-spray throm bolysis were manipulated in groups of rabbits with inferior vena cava throm bosis, and weights of 1-hour residual. thrombus were compared, Variables ev aluated were (i) tPA pulse frequency, (ii) amount of plasminogen used for e nrichment, (iii) tPA concentration and amount, (iv) pulsed versus infused t PA, and (v) admixture versus separation of plasminogen and tPA, RESULTS: With use of 3 mg of tPA and approximate to0.9 mg plasminogen enric hment, efficacy varied directly with pulse frequency over a pulse range of every 15 minutes to every 30 seconds. With use of 30-second pulses of tPA a t a concentration 0.125 mg/mL, efficacy also correlated directly with incre asing plasminogen enrichment up to, but not beyond, approximate to1.8 mg pe r 1.24 g of clot, Optimized methodology yielded 89% lysis in 1 hour, as com pared to 74% lysis previously reported with use of optimized low-concentrat ion (approximate to0.01 mg/mL) tPA alone. Plasminogen enrichment in conjunc tion with low concentrations of tPA, admixture of tPA and plasminogen, and fractionation of the plasminogen enrichment all proved to be nonproductive or counterproductive. CONCLUSION: Optimized in vivo postthrombotic plasminogen enrichment signifi cantly accelerated thrombolysis of experimental clots compared to use of op timized tPA alone.