In Vitro Models for Assessing Transcranial Ultrasound-Enhanced Thrombolysis

Abstract

To the Editor: Contrary to the promising results of recent clinical studies, Pfaffenberger et al conclude from in vitro data that diagnostic ultrasound (US) is not suitable for transcranial enhancement of tissue plasminogen activator (tPA) thrombolysis.1 Their contention is based on surprising control data showing significant clot lysis without tPA and plasminogen and relatively modest increases in clot dissolution with tPA. Interestingly, their reported clot weight loss of 21.8% after 1 hour of incubation in saline alone is much higher than that which they recently reported in another journal using the same methods (2.8%±1.8%2 and 11.0%±3.8%3). Likewise, the effect of tPA alone (27.4%) also differs with earlier results of 19.9%±4.3%3 and 22.7%±9.0%.2 These discrepancies seem important, because a 19.9% effect of tPA alone would have been lower than combined US and recombinant tPA through the skull (26.2%), thus encouraging the authors to positively assess transcranial US thrombolysis. Because clot dissolution is dependent on the amount of plasminogen present and on the amount of tPA available for activation of the plasminogen, little clot lysis should occur during the first 60 minutes of incubation in saline, with or without tPA. To study our hypothesis, we used experimental conditions similar to those of Pfaffenberger et al. 1.5 mL of citrated …