A NEW MODEL FOR QUANTITATIVE IN-VIVO MICROSCOPIC ANALYSIS OF THROMBUSFORMATION AND VASCULAR RECANALIZATION - THE EAR OF THE HAIRLESS (HR HR) MOUSE/

The alteration of rheological blood properties as well as deterioratio n of vascular perfusion conditions and cell-cell interactions are majo r determinants of thrombus formation. Herein, we present an experiment al model which allows for quantitative in vivo microscopic analysis of these determinants during both thrombus formation and vascular recana lisation. The model does not require surgical preparation procedures, and enables for repeated analysis of identical microvessels over time periods of days or months, respectively. After i.v. administration of FITC-dextran thrombus formation was induced photochemically by light e xposure to individual arterioles and venules of the ear of ten anaesth etised hairless mice. In venules, epi-illumination induced rapid throm bus formation with first platelet deposition after 0.59 +/- 0.04 min a nd complete vessel occlusion within 7.48 +/- 1.31 min. After a 24-h ti me period, 75% of the thrombosed venules were found recanalised. Marke d leukocyte-endothelial cell interaction in those venules indicated pe rsistent endothelial cell activation and/or injury, even after an obse rvation period of 7 days. In arterioles, epi-illumination provoked vas omotion, while thrombus formation was significantly (p <0.05) delayed with first platelet deposition after 2.32 +/- 0.22 min and complete ve ssel occlusion within 20.07 +/- 3.84 min. Strikingly, only one of the investigated arterioles was found recanalised after 24 h, which, howev er, did not show leukocyte-endothelial cell interaction. Heparin (300 U/kg, i.v.) effectively counteracted the process of thrombus formation in this model: including both first platelet deposition and vessel oc clusion. We conclude that the model of the ear of the hairless mouse a llows for distinct in vivo analysis of arteriolar and venular thrombus formation/recanalisation, and, thus, represents an interesting tool f or the study of novel antithrombotic and thrombolytic strategies, resp ectively.