Page 83

Karger_ESC London_2013

London, United Kingdom 2013 Cerebrovasc Dis 2013; 35 (suppl 3)1-854 83 18 Experimental studies B 17:50 - 18:00 Efficacy of the novel therapeutic microbubble preparation BR38 in sonothrombolysis (ST) of acute cerebral small artery occlusion N. Schleicher1, A.J. Tomkins2, M. Kampschulte3, F. Yan4, J.-M. Hyvelin5, M. Juenemann6, M. Yeniguen7, M. Kaps8, N.J. Spratt9, T. Gerriets10, M. Nedelmann11 Department of Neurology, Justus Liebig University Giessen, Giessen, GERMANY1,School of Biomedical Science and Pharmacy, University of Newcastle, Newcastle, AUSTRALIA2, Department of Radiology, Justus Liebig University Giessen, Giessen, GERMANY3, Bracco Suisse S.A., Plan-les-Ouates, Geneva, SWITZERLAND4, Bracco Suisse S.A., Plan-les-Ouates, Geneva, SWITZERLAND5, Department of Neurology, Justus Liebig University Giessen, Gies-sen, GERMANY6, Department of Neurology, Justus Liebig University Giessen, Giessen, GER-MANY7, Department of Neurology, Justus Liebig University Giessen, Giessen, GERMANY8, School of Biomedical Science and Pharmacy, University of Newcastle, Newcastle, AUSTRA-LIA9, Department of Neurology, Justus Liebig University Giessen, Giessen, GERMANY10, Depart-ment of Neurology, Justus Liebig University Giessen, Giessen, GERMANY11 Background Clinical and experimental data suggest augmenting effects of microbubble contrast agents con-taining perfluor gases on ST. Previous studies focused on large artery occlusion (MCAO) and on therapeutic use of diagnostic contrast agents. In this study, we tested a novel therapeutic C4F10/N2 containing microbubble preparation (BR38, Bracco Research, Geneva) and the SF6 containing, diagnostically used contrast agent BR1 (SonoVue™) in a rat model of small artery occlusion. The animal model is based on previous studies showing persisting microvascular thrombotic obstruction after reperfusion of 90min MCAO. Methods 36 male WU rats underwent laser Doppler controlled MCA filament occlusion. After 90min reperfusion was induced and rats were randomized into experimental groups with following treatment allocation (n=6): (A) control, (B) tPA, (C) 3 MHz ultrasound (TCCS, MI=1.7) (US) + tPA + BR38 full dose (4x10^8 microbubbles/ml), (D) US + tPA + BR38 1/3 dose, (E) US + tPA + BR1 full dose (equal to full dose BR38), (F) US + tPA + BR1 1/3 dose. After 60min treat-ment rats were sacrificed, brains perfused with radio-opaque substance Microfil™ and removed for micro-CT examination. The vascular volume fraction (VVF) of regions of interest in the left and right MCA territory was determined. Results Micro-CT revealed a significantly reduced VVF within the right MCA territory (expressed as % of left VVF) in groups A and B. In comparison, microbubble augmented treatment improved VVF to a non-significant level in right-left comparison (figure). Effects were comparable for BR38 and BR1 treatment. Hemorrhage was not found on macroscopic examination. Conclusion We found a positive treatment effect for BR38 augmented sonothrombolysis on small artery occlusion. Compared to BR1, BR38 is characterized by a different gas compound, smaller di-ameter of microbubbles and higher stability in circulation. However, treatment effects seen for BR38 and BR1 were comparable with chosen ultrasound setting.


Karger_ESC London_2013
To see the actual publication please follow the link above