Summary
The alteration of rheological blood properties as well as deterioration of vascular
perfusion conditions and cell-cell interactions are major determinants of thrombus
formation. Herein, we present an experimental model which allows for quantitative
in vivo microscopic analysis of these determinants during both thrombus formation
and vascular recanalisation. 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 exposure to individual arterioles and venules
of the ear of ten anaesthetised hairless mice. In venules, epiillumination induced
rapid thrombus formation with first platelet deposition after 0.59 ± 0.04 min and
complete vessel occlusion within 7.48 ±1.31 min. After a 24-h time period, 75% of
the thrombosed venules were found recanalised. Marked leukocyte-endothelial cell interaction
in those venules indicated persistent endothelial cell activation and/or injury, even
after an observation period of 7 days. In arterioles, epi-illumination provoked vasomotion,
while thrombus formation was significantly (p <0.05) delayed with first platelet deposition
after 2.32 ± 0.22 min and complete vessel occlusion within 20.07 ±3.84 min. Strikingly,
only one of the investigated arterioles was found recanalised after 24 h, which, however,
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 occlusion. We conclude that the model of the ear of
the hairless mouse allows for distinct in vivo analysis of arteriolar and venular
thrombus formation/ recanalisation, and, thus, represents an interesting tool for
the study of novel antithrombotic and thrombolytic strategies, respectively.
