Augmented pulse-spray thrombolysis with tPA by early pulsed intrathrombic plasminogen enrichment

PURPOSE: This study was designed to evaluate the efficacy of plasminogen enrichment of subacute thrombus in further accelerating pulse-spray pharmacomechanical thrombolysis (PSPMT) with urokinase (UK) or tissue plasminogen activator (tPA) in a rabbit model. MATERIALS AND METHODS: With use of a subacute rabbit inferior vena cava (IVC) thrombosis model, 78 rabbits were divided into eight groups according to the agents used for thrombolysis: (i) controls (IVC thrombosis, no lysis performed), (ii) pulse-spray thrombolysis with saline only, (iii) PSPMT with UK, (iv) PSPMT with UR, plus interim pulse-spray plasminogen enrichment after 14 minutes, (v) pulse-spray plasminogen enrichment, followed at 10 minutes by PSPMT with UK, (vi) PSPMT with tPA, (vii) PSPMT with tPA, plus interim plasminogen enrichment, and (viii) pulse-spray plasminogen enrichment, followed at 10 minutes by PSPMT with tPA. RESULTS: Intrathrombic pulsed injection of glu-plasminogen after 14 minutes of tPA PSPMT demonstrated significant augmentation of lysis (similar to 31% decrease in residual thrombus) compared with tPA alone (P = .006). Lysis was not augmented significantly when plasminogen was sprayed into thrombus before tPA, or before or after UR. CONCLUSION: Plasminogen enrichment of thrombus after onset of PSPMT with tPA significantly accelerated thrombolysis in a subacute in vivo rabbit model. A clinical trial of this method may be warranted.