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

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 cycles to 7.3±3.2 mmHg/min with 5000 cycles ultrasound pulses (p<0.01). The lytic index was similar between tPA-only [(2.0±0.5)×10−3 mmHg−1min−1] and 5000 cycles without tPA [(2.3±0.5)×10−3 mmHg−1min−1] (p=0.5) but increased [(3.6±0.8)×10−3 mmHg−1min−1] with tPA in conjunction with 5000 cycles ultrasound (p<0.01). In conclusion, SRP restored microvascular perfusion in whole blood and SRP lytic rate in experiments without tPA increased with ultrasound pulse length and efficacy increased with the addition of tPA.

Inertial Cavitation Ultrasound with Microbubbles Improves Reperfusion Efficacy When Combined with Tissue Plasminogen Activator in an In Vitro Model of Microvascular Obstruction

“…The efficacy of MB+US+tPA on sonoreperfusion using whole blood as the perfusate was previously reported by our group (Roos et al 2016). It is worth noting that in vivo homeostasis is hard to reproduce in vitro and our study did not recapitulate the complex dynamic process of thrombus formation-dissolution that occurs in hemostasis in vivo .…”

Therapeutic application of contrast ultrasound in ST elevation myocardial infarction: Role in coronary thrombosis and microvascular obstruction

“…In a later study, using the same model, t-PA was added, resulting in an improvement of microvascular reperfusion. 36 Recently, Belcik et al confirmed these results in a hind limb ischemia mouse model using contrast ultrasound, and the authors observed that this improvement in microvascular flow lasted for more than 24 hours. 37 Even though the exact mechanism underlying this improvement in microvascular flow might not be known, a fair amount of studies with contrast ultrasound have been conducted in order to explore the effect on cellular level and thereby its potential beneficial effect on MVO.…”

“…In a later study, using the same model, t-PA was added, resulting in an improvement of microvascular reperfusion. 36 Recently, Belcik et al confirmed these results in a hind limb ischemia mouse model using contrast ultrasound, and the authors observed that this improvement in microvascular flow lasted for more than 24 hours. 37…”

Drug-Loaded Microbubbles Combined with Ultrasound for Thrombolysis and Malignant Tumor Therapy

“…Studies suggest that ultrasonic radiation combined with drug-loaded microbubbles can dissolve thrombus directly by releasing drugs at the targeted sites, improving the effect of thrombolysis [58]. Ultrasound-enhanced thrombolysis is a promising strategy for the reperfusion therapies of acute stroke and other thrombus diseases [59, 60].…”