Premium
Quantification of microbubble‐induced sonothrombolysis in an ex vivo non‐human primate model
Author(s) -
Hinds Monica T.,
Ammi Azzdine Y.,
Johnson Jennifer,
Kaul Sanjiv
Publication year - 2021
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/jth.15180
Subject(s) - ex vivo , thrombolysis , thrombus , microbubbles , platelet , tissue plasminogen activator , in vivo , biomedical engineering , t plasminogen activator , plasminogen activator , medicine , nuclear medicine , ultrasound , materials science , radiology , biology , myocardial infarction , microbiology and biotechnology
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 111 In‐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 < .001) and with 1.05 MHz at 1.75 MPa and 4.75 MPa ( P < .05) when used with MB and low‐dose rtPA. Although this approach prevented platelet accumulation it did not cause thrombolysis on the device. Conclusions rtPA + MB + US (0.25 and 1.05 MHz) resulted in inhibition of platelet accumulation on the thrombogenic device when moderately high PRAPAs (≥1.75 MPa) were used. These results taken in context with lytic effects of US on myocardial microthrombi and direct effect on myocardial blood flow and function provide direction for the use of therapeutic US in acute coronary syndromes.