Sonoreperfusion Therapy Kinetics in Whole Blood Using Ultrasound, Microbubbles and Tissue Plasminogen Activator

• Published in: Ultrasound in medicine & biology Vol. 42; no. 12; pp. 3001 - 3009
• Main Authors: Roos, Sebastiaan T, Yu, François T, Kamp, Otto, Chen, Xucai, Villanueva, Flordeliza S, Pacella, John J
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 01-12-2016
• Subjects: Cardiac diseases; Fibrinolytic Agents - therapeutic use; Humans; In Vitro Techniques; Kinetics; Microbubbles; Microcirculation; Microvessels; Models, Biological; Phantoms, Imaging; Radiology; Sonothrombolysis; Thromboembolic events; Thrombolytic Therapy - methods; Tissue Plasminogen Activator - therapeutic use; Ultrasonic Therapy - methods; Ultrasound contrast agents; Venous Thrombosis - therapy; Microbubbles; Microcirculation; Thromboembolic events; Sonothrombolysis; Cardiac diseases; Ultrasound contrast agents
• ISSN: 0301-5629; 1879-291X
• DOI: 10.1016/j.ultrasmedbio.2016.08.013

Abstract Coronary intervention for myocardial infarction often results in microvascular embolization of thrombus. Sonoreperfusion therapy (SRP) using ultrasound and microbubbles restored perfusion in our in vitro flow model of microvascular obstruction. In this study, we assessed SRP efficacy using whole blood as the perfusate with and without tissue plasminogen activator (tPA). In a phantom vessel bearing a 40-μm-pore mesh to simulate the microvasculature, microthrombi were injected to cause microvascular obstruction and were treated using SRP. Without tPA, the lytic rate increased from 2.6 ± 1.5 mmHg/min with 1000-cycle pulses to 7.3 ± 3.2 mmHg/min with 5000-cycle ultrasound pulses ( p  < 0.01). The lytic index was similar for tPA-only ([2.0 ± 0.5] × 10−3  mmHg−1  min−1 ) and 5000 cycles without tPA ([2.3 ± 0.5] × 10−3  mmHg−1  min−1 ) ( p  = 0.5) but increased ([3.6 ± 0.8] × 10−3  mmHg−1  min−1 ) with tPA in conjunction with 5000-cycles ultrasound ( p  < 0.01). In conclusion, SRP restored microvascular perfusion in whole blood, SRP lytic rate in experiments without tPA increased with ultrasound pulse length and efficacy increased with the addition of tPA.