22. European Stroke Conference 2 Experimental studies A 14:40 - 14:50 Thrombolysis in experimental cerebral amyloid angiopathy and the risk of secondary in-tracerebral hemorrhage B. Reuter1, S. Grudzenski2, E. Handwerker3, S. Meairs4, P. Heiler5, L. Schad6, M. Staufenbiel7, M.G. Hennerici8, M. Fatar9 Department of Neurology, Universitätsmedizin Mannheim, University of Heidelberg, Mannheim, GERMANY1,Department of Neurology, Universitätsmedizin Mannheim, Univer-sity of Heidelberg, Mannheim, GERMANY2, Department of Neurology, Universitätsmedizin Mannheim, University of Heidelberg, Mannheim, GERMANY3, Department of Neurology, Universitätsmedizin Mannheim, University of Heidelberg, Mannheim, GERMANY4, Computer Assisted Clinical Medicine, Universitätsmedizin Mannheim, University of Heidelberg, Mann-heim, GERMANY5, Computer Assisted Clinical Medicine, Universitätsmedizin Mannheim, University of Heidelberg, Mannheim, GERMANY6, Neuroscience Discovery, Novartis Insti-tutes for BioMedical Research, Basel, SWITZERLAND7, Department of Neurology, Univer-sitätsmedizin Mannheim, University of Heidelberg, Mannheim, GERMANY8, Department of Neurology, Universitätsmedizin Mannheim, University of Heidelberg, Mannheim, GERMA-NY9 Background Intracerebral hemorrhage (ICH) is the most adverse event of thrombolytic therapy in ischemic stroke (IS). In cerebral amyloid angiopathy (CAA), accumulation of amyloid beta results in ce-rebral microbleeds and a higher risk for spontaneous lobar ICH. Although thrombolysis may be performed in CAA-affected patients suffering acute IS, there is still little data available regard-ing the risk for thrombolysis-associated ICH. Methods We investigated the effect of experimental IS and tissue plasmin activator (tPA) treatment in the APP23-transgenic (tg) mouse model of CAA (n=16) and wildtype (wt) littermates (n=14). Focal IS was induced in 26 months old mice by temporal occlusion of the left middle cerebral artery (MCA, filament-model). Animals were treated with 10 mg/kg tPA 30 min after MCA oc-clusion (MCAo). 24 hours after MCAo a functional score was assessed and the mice were sac-rificed for histological analysis. Results APP23-tg mice and controls were equal regarding mortality (3/16 APP-tg, 2/14 wt; p=0.754), histologically assessed infarct volume (32.5±24.9 mm3 vs. 26.2±28.9 mm3; p=0.57) and neu-rological deficit (3±0.6 vs. 2.6±1; p=0.33). However, the APP23 genotype was associated with a higher risk for ICH in the infarct area (9/13 vs. 3/12; p=0.027). For histological evaluation of ICH severity, a score with adjustment for numbers and size was established. We found a posi-tive correlation with infarct size and ICH-severity in APP23-tg mice but not controls (p<0.05). Conclusion To our knowledge, we present the first rodent study evaluating the risk of CAA-associated ICH after stroke thrombolytic therapy. Our results suggest a significantly higher risk for ICH in the genetically CAA-affected brain. So far, severity of ICH increases with infarct size, but was not associated with a higher mortality, or functional deficit. Furthermore, although vascular amy-loid deposits in APP23-tg mice of this age are severe, we observed no ICH outlying of the in-farct area. 14:30-16:00 Oral Session Room 17 Experimental Studies A Chairs: I. Henriques, Portugal and J. Montaner, Spain 1 Experimental studies A 14:30 - 14:40 Hemostatic Therapy in Experimental Intracerebral Hemorrhage Associated with the Di-rect FXa-Inhibitor Rivaroxaban R. Veltkamp1, M. Zorn2, E. Perzborn3, S. Heitmeier4, W. Zhou5 Department of Neurology, University Heidelberg, Heidelberg, GERMANY1,University Heidelberg, Heidelberg, GERMANY2, Bayer Pharma, Wuppertal, GERMANY3, Bayer Pharma, Wuppertal, GERMANY4, Department of Neurology, University Heidelberg, Heidelberg, GER-MANY5 Background: Rivaroxaban has recently been approved for stroke prevention in atrial fibrillation. However, lack of an effective antidote represents a major concern in the event of intracerebral hemorrhage (ICH). The aims of the present study were to establish a murine model of ICH as-sociated with rivaroxaban, and to examine the effectiveness of different hemostatic factors in preventing excess hematoma expansion. Methods: In C57BL/6 mice receiving 10 or 30mg/ kg rivaroxaban by gastric gavage, plasma concentration, prothrombin time and coagulation factor’s activities were measured repeatedly. Thirty minutes after inducing ICH by intrastria-tal collagenase-injection, mice received an intravenous injection of either saline, prothrombin complex concentrate (PCC, 100U/kg), murine fresh frozen plasma (FFP, 200μL), or recombi-nant human Factor VIIa (FVIIa, 1mg/kg). ICH volume was quantified on brain cryosections 24h later. Results: Rivaroxaban (30mg/kg) substantially increased the hematoma volume in ICH induced by 0.06U collagenase. PCC, FFP, or FVIIa prevented excess hematoma expansion caused by anticoagulation. Prevention of hematoma expansion by PCC was dose-dependent. None of the three agents completely corrected the prolonged prothrombin time, although they restored the activities of deficient FII and X. Conclusions: PCC, FVIIa and FFP can prevent excess intracerebral hematoma expansion in a murine ICH model associated with rivaroxaban. The efficacy and safety of this reversal strategy must be further evaluated in clinical studies. 56 © 2013 S. Karger AG, Basel Scientific Programme
Karger_ESC London_2013
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