s-5682 and Ischemia

Daflon 500 mg (S-5682) is a purified, micronized flavonoid fraction containing 90% diosmin and 10% hesperidin that is currently used to treat chronic venous insufficiency and hemorrhoidal disease. Thus, it seemed of interest to evaluate the effects of S-5682 on ischemia/reperfusion, ie, the changes in mean internal diameter and blood flow of arterioles and venules and the functional capillary density (FCD) during reperfusion after ninety minutes of total ischemia in the hamster cheek pouch microvasculature. Different doses of S-5682 (5, 20, 80, and 160 mg/kg body weight/day), suspended in 10% lactose solution or vehicle (10% lactose) were administered orally to male hamsters for ten days twice a day. The cheek pouch preparation was placed under an intravital microscope coupled to a closed-circuit TV system. A ninety-minute local ischemia was obtained by a cuff mounted around the neck of the everted pouch where it left the mouth of the hamster. Mean arteriolar and venular internal diameters were determined by means of an image-shearing device, IPM model 907; red blood cell (RBC) velocity was measured by the dual-slit photometric technique; microvessel volume flow was calculated from diameters and RBC velocities; and FCD was defined as the number of red-cell-perfused capillaries per observation field. During reperfusion, placebo-treated animals showed significant vasodilatation concomitant with a decrease in blood flow and FCD compared with preischemic values and an impairment of the myogenic response. In S-5682-treated animals, there was a significant dose-dependent improvement in all these parameters including the myogenic tonus. These results clearly demonstrated that oral administration of different doses of S-5682 for ten days improved the microvascular reactivity and FCD after ischemia/reperfusion in a dose-dependent fashion in the hamster cheek pouch microvasculature.

Topics: Animals; Arterioles; Cheek; Cricetinae; Diosmin; Dose-Response Relationship, Drug; Drug Combinations; Flavonoids; Hesperidin; Ischemia; Male; Mesocricetus; Microcirculation; Regional Blood Flow; Reperfusion; Vasomotor System; Venules

1. The effects of a purified micronized flavonoid fraction (S5682) on mean internal diameter and blood flow 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-1 day-1) 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 cuff 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 flow was calculated from diameters and RBC velocities. FCD, defined as the number of capillaries with flowing blood per field of observation, was also assessed. 4. During reperfusion, placebo-treated animals showed a significant vasodilatation, a decrease in blood flow 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 beneficial therapeutic effect in chronic venous insufficiency where oxidative stress is involved in the pathological mechanism.

Topics: Administration, Oral; Animals; Arterioles; Cheek; Cricetinae; Diosmin; Drug Combinations; Hesperidin; Ischemia; Male; Regional Blood Flow; Reperfusion; Venules