title: In vitro sonothrombolysis of human blood clots with BR38 microbubbles.
abstract: Microbubble-mediated sonothrombolysis is a promising approach for ischemic stroke treatment. The aim of this in vitro study was to evaluate a new microbubble (MB) formulation (BR38) for sonothrombolysis and to investigate the involved mechanisms. Human whole-blood clots were exposed to different combinations of recombinant tissue plasminogen activator (rtPA), ultrasound (US) and MB. Ultrasound at 1.6 MHz was used at 150, 300, 600 and 1000 kPa (peak-negative pressure). Thrombolysis efficacy was assessed by measuring clot diameter changes during 60-min US exposure. The rate of clot diameter loss (RDL) in μm/min was determined and clot lysis profiles were analyzed. The most efficient clot lysis (5.9 μm/min) was obtained at acoustic pressures of 600 and 1000 kPa in combination with MB and a low concentration of rtPA (0.3 μg/mL). This is comparable with the rate obtained with rtPA at 3 μg/mL alone (6.6 μm/min, p > 0.05). Clot lysis profiles were shown to be related to US beam profiles and microbubble cavitation.
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Geneva, Switzerland. benedicte.petit@unige.ch
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Petit
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Gaud
authors.forename: Delphine
authors.initials: D
authors.lastname: Colevret
authors.forename: Marcel
authors.initials: M
authors.lastname: Arditi
authors.forename: Feng
authors.initials: F
authors.lastname: Yan
authors.forename: François
authors.initials: F
authors.lastname: Tranquart
authors.forename: Eric
authors.initials: E
authors.lastname: Allémann
mesh_terms: D001777:Blood Coagulation / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects*; D003287:Contrast Media / Q000528:radiation effects*; D006801:Humans; D045423:Microbubbles / Q000627:therapeutic use*; D015912:Thrombolytic Therapy; D014464:Ultrasonic Therapy / Q000379:methods*
chemical_list: D003287:Contrast Media