Article révisé par les pairs
Résumé : BACKGROUND/OBJECTIVES: We examined the applicability of contrast-enhanced ultrasound (CEUS) for imaging of murine deep vein thrombosis (DVT) and measured the effects of enoxaparin, ticagrelor, and P2Y12 receptor deficiency in vivo. METHODS: DVT was induced by exposure to ferric chloride or ligation of the infrarenal vena cava of C57BL/6 mice after pretreatment with enoxaparin, ticagrelor, or vehicle and in P2Y12 -/- mice. Initial thrombus growth was visualized by intravital microscopy. Thrombi were weighed and examined by immunohistochemistry. CEUS was performed with a standard ultrasound system (Vivid 7, GE Healthcare) in the open abdominal cavity after injection of stabilized sulphur hexafluoride microbubbles. RESULTS: Incubation with ferric chloride resulted in non-occluding platelet-containing thrombus growth within 15-25 min. Sham-operated mice, enoxaparin-, and ticagrelor-pretreated wild-type and P2Y12 -/- mice developed only small thrombi. After injection of the contrast agent, growing thrombi delineated clearly as negative contrast in CEUS. Thrombus size in CEUS after 25 minutes was significantly smaller in enoxaparin- (0.3±0.1mm(2) ) and ticagrelor-treated (0.5±0.1mm(2) ) wild-type and in P2Y12 -/- mice (0.4±0.1mm(2) ) as compared to vehicle-treated wild-type mice (2.0±0.3mm(2) ) in the maximal sagittal plane (p < 0.001, n = 5-10). CEUS-derived thrombus size correlated linearly with thrombus weight and also reflected the extent of ligation-induced DVT. CONCLUSIONS: CEUS allowed the real-time quantification of DVT in living mice. Genetic and pharmacologic antithrombotic interventions were well reflected by CEUS and suggested an important role of the platelet P2Y12 receptor in early DVT formation. © 2013 International Society on Thrombosis and Haemostasis.

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