Guided longer pulses from a diagnostic ultrasound and intraclot microbubble enhanced catheter-directed thrombolysis in vivo

J Thromb Thrombolysis. 2017 Jul;44(1):48-56. doi: 10.1007/s11239-017-1500-6.

Abstract

The mechanism of ultrasound thrombolysis (UT) is generally attributed to cavitation. The insufficiency of microbubbles (MB) to serve as cavitation nuclei in the vessel-obstructing thrombi significantly reduces the effectiveness of UT. Taking advantage of the widely performed catheter-directed therapy (CDT), in a thrombo-embolized rabbit IVC model with a simultaneous catheter directed rt-PA thrombolysis procedure, guided moderate mechanical index longer pulses from a modified diagnostic ultrasound transducer, combined with an intraclot infusion of MB, significantly accelerated the thrombolysis process. The higher thrombolysis efficacy score and consistent elevated post-treatment plasma concentration level of D-Dimer, a product of fibrinolysis, both indicated the superiority of CDT + UT over CDT/UT alone. Pathologic examination of the treated occluded IVC segments revealed an almost complete dissolution of the thrombi treated with CDT + UT. There was no evidences of thrombo-embolism or local thrombus formation in the cardiac-pulmonary vessels. Combined with intraclot infusion of MB, guided longer pulse ultrasound from a diagnostic transducer is able to safely and significantly improve a catheter-directed thrombolysis procedure. It thus has the potential to achieve earlier clot removal, administration of a lower dosage of thrombolytic agent and, consequently, a lower incidence of thrombolysis-related side effects.

Keywords: Catheter-directed therapy; Microbubbles; Thrombolysis; Ultrasound.

MeSH terms

  • Animals
  • Catheterization* / instrumentation
  • Catheterization* / methods
  • Contrast Media / pharmacology*
  • Echocardiography, Doppler, Color*
  • Fibrin Fibrinogen Degradation Products / metabolism
  • Fibrinolysis*
  • Male
  • Mechanical Thrombolysis* / instrumentation
  • Mechanical Thrombolysis* / methods
  • Microbubbles*
  • Rabbits

Substances

  • Contrast Media
  • Fibrin Fibrinogen Degradation Products
  • fibrin fragment D