These results indicate that in this model chronic elevation of venous pressure is associated with an inflammatory reaction in venous valves, a process that may lead to their dysfunction, reflux, and upstream elevation of venous pressure. These effects are mitigated by the anti-inflammatory micronized purified flavonoid fraction in a dose dependent manner.

1 The e ects of a puri®ed micronized¯avonoid fraction (S5682) on mean internal diameter and blood ow of arterioles and venules, as well as the functional capillary density (FCD) were evaluated in the hamster cheek pouch microvasculature before and after 90 min of total ischaemia. 2 Male hamsters were treated for ten days, twice a day, with oral doses of S5682 (5, 20, 80 and 160 mg kg 71 day 71 ) or placebo (10% lactose solution). The cheek pouch preparation was placed under an intravital microscope coupled to a closed circuit TV system. Local ischaemia was obtained by a cu mounted around the neck of the everted pouch where it leaves the mouth of the hamster. 3 Measurements were performed before ischaemia, at the onset of reperfusion and 10, 20, 30, 45 and 60 min thereafter. Diameters were measured by means of an image shearing device. Red blood cell (RBC) velocity was analysed by use of the dual-slit photometric technique. Blood¯ow was calculated from diameters and RBC velocities. FCD, de®ned as the number of capillaries with¯owing blood per ®eld of observation, was also assessed. 4 During reperfusion, placebo-treated animals showed a signi®cant vasodilatation, a decrease in blood ow and FCD and S5682-treated animals showed a clear trend, dose-dependent, towards maintaining these parameters closer to the value found before ischaemia. 5 In conclusion, our results indicate that S5682 improves the microvascular reactivity and FCD after ischaemia/reperfusion. These data suggest that S5682 could function as an antioxidant, which may explain its bene®cial therapeutic e ect in chronic venous insu ciency where oxidative stress is involved in the pathological mechanism.

These results suggested that microvascular occlusion in venules with elevation of the micropressure followed by reperfusion is a highly cytotoxic process in the rat mesentery which can be attenuated by MPFF pretreatment.

Oral administration of S-5682 (Daflon 500 mg, 90% diosmin, 10% hesperidin) inhibits oxidant-induced increase in macromolecular permeability in the postcapillary venules of the hamster cheek pouch microcirculation. In this study, the effect of S-5682 on leukocyte-endothelium interaction was evaluated using the same experimental model. Hamsters kept on a standard diet were divided into 5 groups (n = 6) and treated orally, twice a day, with placebo (10% lactose solution), S-5682, 5, 20 or 80 mg/kg/day (suspended in 10% lactose solution) or α-tocopherol, 1 mg/kg/day, for 10 days prior to the oxidant challenge with tert-butylhydroperoxide (TBOOH). Topical application of TBOOH (10^–4 M for 5 min) to hamsters given acridine orange prior to TBOOH resulted in increases in the number of rolling and sticking (no movement for at least 30 s) leukocytes in postcapillary venules. No changes in the number of rolling leukocytes could be observed in the treated groups compared with the placebo group (p > 0.05). On the contrary, leukocyte adhesion was inhibited in groups treated with S-5682 (5, 20 and 80 mg/kg/day) or α-tocopherol: placebo 105 ± 3/6 mm² (mean ± SEM); S-5682, 5 mg/kg/day 68 ± 3/6 mm² (p < 0.01), 20 mg/kg/day 55 ± 3/6 mm² (p < 0.001) and 80 mg/ kg/day 39 ± 2/6 mm² (p < 0.001) and α-tocopherol 36 ± 1/6 mm² (p < 0.001). The inhibition of oxidant-induced leukocyte adhesion by S-5682 was similar to that seen for ischemia-reperfusion and the higher dose of S-5682 was as effective as α-tocopherol in inhibiting it.