Roesken F, Ruecker M, Vollmar B, Boeckel N, Morgenstern E, Menger M D
Institute for Clinical & Experimental Surgery, University of Saarland, Homburg/Saar, Germany.
Thromb Haemost. 1997 Nov;78(5):1408-14.
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, epi-illumination 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.
血液流变学特性的改变以及血管灌注条件和细胞间相互作用的恶化是血栓形成的主要决定因素。在此，我们提出一种实验模型，该模型允许在血栓形成和血管再通过程中对这些决定因素进行定量的体内显微镜分析。该模型不需要手术准备程序，并且能够在数天或数月的时间段内对相同的微血管进行重复分析。静脉注射异硫氰酸荧光素标记的葡聚糖后，通过光照射十只麻醉的无毛小鼠耳部的单个小动脉和小静脉，以光化学方式诱导血栓形成。在小静脉中，落射照明诱导快速血栓形成，0.59±0.04分钟后首次出现血小板沉积，7.48±1.31分钟内血管完全闭塞。24小时后，发现75%的血栓形成小静脉实现再通。即使在观察7天后，这些小静脉中明显的白细胞-内皮细胞相互作用仍表明内皮细胞持续激活和/或损伤。在小动脉中，落射照明引起血管运动，而血栓形成明显延迟（p<0.05），2.32±0.22分钟后首次出现血小板沉积，20.07±3.84分钟内血管完全闭塞。令人惊讶的是，2,4小时后仅发现一条被研究的小动脉实现再通，然而，该小动脉未显示白细胞-内皮细胞相互作用。肝素（300 U/kg，静脉注射）在该模型中有效对抗血栓形成过程，包括首次血小板沉积和血管闭塞。我们得出结论，无毛小鼠耳部模型允许对小动脉和小静脉血栓形成/再通进行独特的体内分析，因此分别代表了研究新型抗血栓和溶栓策略的有趣工具。
