Drug Discov Ther. 2022;16(5):233-239. (DOI: 10.5582/ddt.2022.01064)

In vitro study about prevention of vascular reocclusion by low intensity ultrasonic irradiation

Sawaguchi Y, Wang Z, Yamamoto H, Nakata N


For the treatment of acute ischemic stroke, the current standard of care is thrombolysis by the administration of intravenous (IV) recombinant tissue-type plasminogen activator (rt-PA). Although this approach is proven to be effective, reocclusion within 24 hours occurs in about 20% of patients who receive recanalization by rt-PA. In addition, the administration of anticoagulants within 24 hours after IV rt-PA increases the risk of intracranial hemorrhage; therefore, treatment with anticoagulants is contraindicated in this population. To address the need for an approach to sustain the effects of thrombolysis prevent blood vessel reocclusion without the use of anticoagulants, this study proposes a novel method using a low-intensity ultrasound (US) irradiation. An in vitro thrombus-growth model, in a latex rubber container was developed to study the effect of thrombusgrowth suppression by US irradiation at 500 kHz in a 37°C water bath. The US acoustic intensity was set at or below 0.72 W/cm2, which is the maximum allowed for noninvasive acoustic irradiation. Low-intensity US irradiation of the thrombus-growth model resulted in a remarkable suppression of thrombus growth (100.22 ± 10.1 mg vs. 50.22 ± 5.3 mg, p < 0.0001), and the clot-growth inhibition depended logarithmically on acoustic intensity. Thrombus growth can be suppressed by lowintensity US irradiation, opening a new way to combat vascular reocclusion after rt-PA treatment of acute ischemic stroke.

KEYWORDS: Acute ischemic stroke, reocclusion, prevention, non-invasive ultrasound, recombinant tissue-type plasminogen activator

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