Effects of the phlebotropic drug Daflon 500 mg on postischemic reperfusion injury in striated skin muscle: a histomorphologic study in the hamster.
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.
Pickelmann
S
S
Institute for Surgical Research, Klinikum Grosshadern, Munich, Germany.
Nolte
D
D
Leiderer
R
R
Möllmann
M
M
Schütze
E
E
Messmer
K
K
D000818:Animals; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D006224:Cricetinae; D004145:Diosmin / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D007962:Leukocytes / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008297:Male; D008647:Mesocricetus; D008854:Microscopy, Electron; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000187:drug effects / Q000293:injuries; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology; D012867:Skin / Q000098:blood supply* / Q000187:drug effects / Q000293:injuries
D004145:Diosmin; C021443:leukocyte esterase; D002265:Carboxylic Ester Hydrolases