Effects of the phlebotropic drug Daflon 500 mg on postischemic reperfusion injury in striated skin muscle: A histomorphologic study in the hamster

• Published in: The Journal of laboratory and clinical medicine 1999-11, Vol.134 (5), p.536-545
• Main Authors: Pickelmann, Sven, Nolte, Dirk, Leiderer, Rosemarie, Möllmann, Matthias, Schütze, Elke, Messmer, Konrad
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Carboxylic Ester Hydrolases - metabolism; Cardiovascular system; Cell Movement - drug effects; Cricetinae; Diosmin - administration & dosage; Diosmin - pharmacology; Disease Models, Animal; Leukocytes - drug effects; Leukocytes - enzymology; Leukocytes - pathology; Male; Medical sciences; Mesocricetus; Microscopy, Electron; Muscle, Skeletal - blood supply; Muscle, Skeletal - drug effects; Muscle, Skeletal - injuries; Pharmacology. Drug treatments; Reperfusion Injury - drug therapy; Reperfusion Injury - pathology; Skin - blood supply; Skin - drug effects; Skin - injuries; Vascular wall
• ISSN: 0022-2143; 1532-6543
• DOI: 10.1016/S0022-2143(99)90176-2

The objective of this study was to investigate the effects of the purified, micronized, flavonoid fraction Daflon 500 mg (S 5682, 90% diosmin and 10% hesperidin) on tissue damage and leukocyte emigration in striated skin muscle after ischemia-reperfusion, as assessed by histomorphometric analysis. The experimental model used was the transparent dorsal skin fold chamber in the awake Syrian golden hamster. Sixty-four animals were randomly allotted to two treatment groups and time points of investigation. Animals were fed with 30 mg kg−1 body weight Daflon 500 mg (n = 32) or its vehicle, 5% Arabic gum solution (n = 32), as control 8 hours before ischemia. Before induction of a tourniquet ischemia of 4 hours' duration and at 0.5, 2, and 24 hours of reperfusion, tissue sections were preserved for light and electron microscopic analysis (n = seven or eight animals per time point). The number of intravascular and extravascular leukocytes was determined by light microscopic analysis of esterase-positive leukocytes. For quantitative analysis of ischemia-induced endothelial cell damage, the endothelial thickness of capillaries was calculated by a computer-assisted imaging system, whereas the ischemic tissue damage was assessed by means of a score system (grade 0–3) by an independent investigator. The number of emigrated leukocytes was significantly reduced in Daflon 500 mg-treated animals compared with numbers found in control animals. The histomorphologic muscle fiber damage increased after reperfusion in both groups but was significantly reduced in the Daflon 500 mg-treated animals 2 and 24 hours after reperfusion. These results suggest that the emigration of leukocytes plays an important role in the development of postischemic reperfusion injury of striated skin muscle.