Enhanced Clot Dissolution In Vitro by 1.8-MHz Pulsed Ultrasound

Clinical studies of acute stroke patients have shown that the use of high frequency, low energy transcranial “diagnostic” ultrasound (US) enhances thrombolysis (sonothrombolysis). In contrast, a previous in vitro study using a clot preparation with coagulation induced by recalcification failed to reproduce an effect of “diagnostic” transcranial US on thrombolysis. We sought to evaluate this contradiction in an in vitro model with modified clot preparation. The efficacy of 1.8-MHz pulsed-wave (PW) ultrasound (US) emitted by a commercial probe on thrombolysis was tested. Whole blood clots from 0.5-mL venous blood samples were insonated for 1 h through a human temporal bone, using 1.8-MHz PW US emitted by a diagnostic device. The experiment was performed with or without recombinant tissue-type plasminogen activator (rt-PA) at a concentration of 10 μg/mL. Thrombolysis was measured by means of clot weight loss after 1 h of insonation. A reduction in thrombus weight occurred when US was used in combination with rt-PA, compared with rt-PA alone (78.7% ± 2.1% versus 70.8% ± 4.1%, p ≤ 0.0001). Repetition of the experiment produced identical results (76.9% ± 2.5%, compared with control, p = 0.001). Even without rt-PA, US was effective (41.0% ± 1.7% versus 36.7% ± 3.7%, p = 0.04). The results of this in vitro study support the clinical observation that diagnostic transcranial US, with or without rt-PA, enhances thrombolysis. (E-mail: juergeneggers@gmx.net)