Effects of the phlebotropic drug Daflon 500 mg on postischemic microvascular disturbances in striated skin muscle: An intravital microscopic study inthe hamster

The objective of this study was to investigate the effects of the micronize d purified flavonoid fraction Daflon 500 mg (90% diosmin and 10% hesperidin ) on I/R-induced microvascular leukocyte-endothelium interaction and leakag e of the high molecular weight plasma tracer FITC-dextran (relative molecul ar mass, 150 kd) as assessed in the striated skin muscle of the dorsal skin ford chamber model in the hamster. Intravital fluorescence microscopy was used for analysis of microvascular perfusion, leukocyte-endothelium interac tion, and macromolecular leakage of FITC-dextran 150 kd in the striated ski n muscle of the hamster. A tourniquet ischemia of 4 hours' duration was ind uced followed by reperfusion. Animals were treated with an oral administrat ion of Daflon 500 mg (n = six) or its vehicle (5% Arabic gum solution, n = six) for 8 days at a daily dose of 30 mg/kg body weight, Measurements in th e microcirculation were made before the 8-day feeding protocol before induc tion of ischemia and at 0.5, 2, and 24 hours of reperfusion, In the absence of I/R, no differences in microvascular perfusion, leukocyte-endothelium i nteraction, and macromolecular leakage were found in Daflon 500 mg and vehi cle-treated control animals before and after administration of the drugs. i nduction of ischemia and reperfusion, however, elicited a significant incre ase in venular leukocyte rolling and sticking in vehicle-treated animals, w hich was accompanied by enhancement of leakage of FITC-dextran 150 kd into the perivascular tissue, Treatment with Daflon 500 mg had no effect on post ischemic leukocyte rolling and sticking, and macromolecular leakage of FITC -dextran 150 kd from arterioles and postcapillary venules was significantly reduced. These data indicate that Daflon 500 mg preserves the endothelial barrier function of striated skin muscle arterioles and venules after I/R, which appears to be independent of an action on postischemic intravascular leukocyte rolling and sticking.