Quantification of microbubble-induced sonothrombolysis in an ex vivo non-human primate model

Abstract

Background: In vitro studies with ultrasound (US) and microbubbles (MB) have reported that sono-thrombolysis can be achieved at high peak rarefactional acoustic pressure amplitudes (PRAPAs) using 0.25 and 1.05 MHz US frequencies. Objective: The aim of the current study was to determine if these parameters work on an ex vivo physiological model of thrombosis. Methods: A thrombogenic device was placed in an ex vivo chronic arteriovenous shunt in juvenile baboons. Platelet accumulation was measured by dynamic imaging of the device and the 10 cm thrombus tail with 111In-labeled platelets. After 15 minutes of thrombus formation, treatment with either low-dose recombinant tissue plasminogen activator (rtPA) or low-dose rtPA + MB+US was performed for 20 minutes. Four US settings at 0.25% duty cycle were used: 0.25 MHz at PRAPAs of 1.20 and 2.20 MPa, and 1.05 MHz at 1.75 and 4.75 MPa. Results: Platelet accumulation was not inhibited by low-dose rtPA or MB with US alone. Platelet accumulation was significantly reduced with 0.25 MHz US at 2.20 PRAPA (P