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London, United Kingdom 2013 8 Translational stroke research 9:40 - 9:50 DIRECT THROMBIN INHIBITOR DABIGATRAN AS TREATMENT IN EXPERI-MENTAL INTRACEREBRAL HEMORRHAGE BRAIN MODEL S. Illanes1, C. Urrutia2, F. Vial3, P. Congett4 Instituto de Ciencias, Universidad del Desarrollo-Clínica Alemana, Santiago, CHILE1,In-stituto de Ciencias, Universidad del Desarrollo-Clínica Alemana, Santiago, CHILE2, Instituto de Ciencias, Universidad del Desarrollo-Clínica Alemana, Santiago, CHILE3, Instituto de Cien-cias, Universidad del Desarrollo-Clínica Alemana, Santiago, CHILE4 Background and Purpose In intracerebral hemorrhage, blood–brain barrier leakage of serum constituents such as throm-bin might exert a direct toxic effect on brain parenchyma. Thrombin has been shown to cause neuronal cell death both in vitro and in hemorrhage models in vivo. In hemorrhagic stroke models, continuous release of activated thrombin from existing clots would exert severe dam-age to the brain tissue, whereas infusion of argatroban, a direct inhibitor of thrombin, showed a reduced level of perihematomal infarction. In addition, previous studies have related thrombin to blood–brain barrier damage and edema formation. We aim to use the commercially available direct thrombin inhibitor Dabigatran etaxilate (Pradaxa®) as a treatment in a experimental ICH mice model. Methods In the ICH mice C57BL/6 model, there is no further hematoma expansion after 6 hours since the collagenase injection. Six hours after the ICH induction, mice received an intraperitoneal injection of dabigatran etaxilate (9.0 mg/kg) or saline. Behavioural tests, physiological param-eters, hematoma volume and hemispheric water content was quantified on brains 24h after the ICH induction. A second group of animal received dabigatran etaxilate (9.0 mg/kg) or saline 6 and 24 hours after the ICH induction. Outcome was measured 48 hours after the ICH induction in this set of animals. Results We observed dabigatran anticoagulatory effect for more than 8 hours measured by an in vivo assay (lateral vein bleeding time). No further hematoma expansion was observed in dabigatran treatment group compared to controls. Water content was significantly reduced in dabigatran treatment group 24h (73.3% versus 78.7%. p<0.001. n=10 per group) and 48h (77.2% vs. 79.2. p=0.02 n=9 per group) after ICH induction. Conclusion Administration of dabigatran etaxilate (Pradaxa ®) 6 and 24h after ICH induction reduces peri-hematoma edema development in the collagenase ICH mice model without further hema-toma enlargement. This might be a good candidate for a clinical phase II study. Cerebrovasc Dis 2013; 35 (suppl 3)1-854 31 TABLE 1. Clinical and demographic data in MNC group. No Age/ sex Area of infarct No of cells baseline 24 weeks 78 weeks 156 weeks FM (/66) mBI (/100) FM (/66) mBI (/100) FM (/66) mBI (/100) FM (/66) m BI (/100) 1 32/ M Lt fronto parietal 56 x 106 22 52 48 82 50 82 54 86 M Rt frontal 54 x 106 14 32 28 65 30 67 32 74 2 62/ 3 49/ M Rt fronto parietal 50 x106 14 43 28 84 30 84 34 84 M Rt temporal 58 x 106 24 52 54 90 56 9 60 92 4 42/ 5 55/ M Rt fronto parietal 57 x 106 22 50 44 72 46 80 49 80 6 60/ M Rt striato capsular 55x 106 17 50 40 85 42 85 45 87 M Lt PLIC 56 x 106 22 58 38 78 40 80 42 82 7 42/ M Lt parietal 58 x 106 44 72 60 98 60 98 61 98 8 35/ 9 40/ M Rt striato capsule 55 x 106 22 55 49 84 51 84 54 88 10 32/ F Lt frontal/ parietal 52 x 106 12 40 28 60 30 62 32 65 M Rt parietal 53 x 106 17 43 39 82 39 82 43 86 11 50/ 12 60/ M Lt frontal temporal/ parietal 52 x 106 11 38 28 64 30 65 32 70 Me an 46.5 54.6 x 106 20.0 8 48.75 33.5 68.75 42 73.1 44.8 82.6 Graph 1 between MNC and control group showing p values. s


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