Augmented Pulse-Spray Thrombolysis with tPA by Early Pulsed Intrathrombic Plasminogen Enrichment

Abstract

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. 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 UK, 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. Intrathrombic pulsed injection of glu-plasminogen after 14 minutes of tPA PSPMT demonstrated significant augmentation of lysis (approximately 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 UK. 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.