EFFECT OF RECOMBINANT TISSUE PLASMINOGEN ACTIVATOR AND 120-KHZ ULTRASOUND ON PORCINE INTRACRANIAL THROMBUS DENSITY

Surgical intervention for the treatment of intracerebral hemorrhage (ICH) has been limited by inade-quate lysis of the target thrombus. Adjuvant transcranial ultrasound exposure is hypothesized to improve throm-bolysis, expedite hematoma evacuation and improve clinical outcomes. A juvenile porcine intracerebral hemorrhage model was established by direct infusion of autologous blood into the porcine white matter. Thrombi were either not treated (sham) or treated with recombinant tissue plasminogen activator alone (rt-PA only) or in combination with pulsed transcranial 120-kHz ultrasound (sonothrombolysis). After treatment, pigs were eutha-nized, the heads frozen and sectioned and the thrombi extracted. D-Dimer and thrombus density assays were used to assess degree of lysis. Both porcine and human D-dimer assays tested did not have sufficient sensitivity to detect porcine D-dimer. Thrombi treated with rt-PA with or without 120-kHz ultrasound had a significantly lower density compared with sham-treated thrombi. No enhancement of rt-PA-mediated thrombolysis was noted with the addition of 120-kHz ultrasound (sonothrombolysis). The thrombus density assay revealed thrombolytic efficacy caused by rt-PA in an in vivo juvenile porcine model of intracerebral hemorrhage. Transcranial sono-thrombolysis did not enhance rt-PA-induced thrombolysis, likely because of the lack of exogenous cavitation nuclei. (E-mail: hollanck@mail.uc.edu) (c) 2022 Published by Elsevier Inc. on behalf of World Federation for Ultrasound in Medicine & Biology.

Automated summary

Transcranial ultrasound exposure was hypothesized to improve thrombolysis for intracerebral hemorrhage (ICH). However, the study found no enhancement of rt-PA-induced thrombolysis with the addition of ultrasound, likely due to the lack of exogenous cavitation nuclei. This research has important implications for surgical intervention in ICH.