MICROVASCULAR REACTIVITY AFTER ISCHEMIA REPERFUSION IN THE HAMSTER-CHEEK POUCH - BENEFICIAL-EFFECTS OF DIFFERENT ORAL DOSES OF S-5682 (DAFLON 500 MG)/

Daflon 500 mg (S-5682) is a purified, micronized flavonoid fraction co ntaining 90% diosmin and 10% hesperidin that is currently used to trea t chronic venous insufficiency and hemorrhoidal disease. Thus, it seem ed of interest to evaluate the effects of S-5682 on ischemia/reperfusi on, ie, the changes in mean internal diameter and blood flow of arteri oles and venules and the functional capillary density (FCD) during rep erfusion after ninety minutes of total ischemia in the hamster cheek p ouch microvasculature. Different doses of S-5682 (5, 20, 80, and 160 m g/kg body weight/day), suspended in 10% lactose solution or vehicle (1 0% lactose) were administered orally to male hamsters for ten days twi ce a day. The cheek pouch preparation was placed under an intravital m icroscope coupled to a closed-circuit TV system. A ninety-minute local ischemia was obtained by a cuff mounted around the neck of the everte d pouch where it left the mouth of the hamster. Mean arteriolar and ve nular 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 calcu lated from diameters and RBC velocities; and FCD was defined as the nu mber of red-cell-perfused capillaries per observation field. During re perfusion, placebo-treated animals showed significant vasodilatation c oncomitant with a decrease in blood flow and FCD compared with preisch emic values and an impairment of the myogenic response. In S-5682-trea ted 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 mi crovasculature.