Microvascular consequences of thrombosis in small venules: An in vivo microscopic study using a novel model in the ear of the hairless mouse

Little is known of the development of chronic microvascular alterations fol lowing small vessel thrombosis, which is probably due to the lack of approp riate experimental models. Herein we report the first results on thrombosis -associated longterm changes of microvascular permeability and vessel tortu osity and diameter and blood perfusion using the ear of the hairless mouse, and intravital fluorescence microscopy. Thrombosis was induced photochemic ally in small venules (diameter: 75 to 100 mu m) using light/dye exposure ( fluorescein isothiocyanate-dextran 150,000), and the microcirculation compr omised by the blockade of blood drainage was analyzed before and 30 minutes after induction of thrombosis as well as repeatedly over a 28-day observat ion period. Thrombus formation resulted in a marked increase (p<0.05) of mi crovascular permeability (0.85+/-0.11) when compared with baseline values ( 0.46+/-0.04). Permeability remained elevated (p<0.05) at days 1 (0.67+/-0.0 7), 3 (0.58+/-0.02), and 7 (0.60+/-0.06), but returned to normal after 28 d ays (0.43+/-0.03). Tortuosity, diameter, and red blood cell velocity of ven ular segments, located upstream of thrombus formation, were found unchanged during the entire 28-day observation period. This was probably due to the fact that blood flow from the thrombosis-affected tissue was frequently dra ined into nonaffected tissue via preexisting "through-fare" channels, servi ng as venulo-venular collaterals. In accordance, in 10 to 20% of these venu lar segments the direction of blood perfusion was found changed, while thos e changes were only rarely observed in venular vessel segments of the nonth rombotic contralateral ears. We conclude that thrombosis in small cutaneous venules is primarily characterized by an increased vascular permeability, reflecting an inflammatory response, similar to what is known from thrombop hlebitis in patients. The model presented herein may be a versatile tool to study pathogenesis of chronic microcirculatory derangements in microthromb osis and their prevention by novel therapeutic strategies. (C) 2000 Elsevie r Science Ltd. All rights reserved.