Reduction of postischemic reperfusion injury by the vasoactive drug buflomedil.
The effect of buflomedil on postischemic reperfusion injury was studied in the dorsal skin fold chamber preparation of awake hamsters. Microvascular events were investigated in the striated skin muscle by means of intravital fluorescence microscopy prior to 4 h of pressure-induced ischemia and 30 min, 2 and 24 h after reperfusion. In untreated control animals, ischemia and reperfusion provoked marked leukocyte sticking and macromolecular leakage while functional capillary density was reduced. Treatment with buflomedil (3 mg/kg b.w. in 0.3 ml saline, administered as bolus of 0.1 ml 10 min prior to release of ischemia followed by i.v. infusion of 0.2 ml during the first 20 min of reperfusion) significantly reduced leukocyte sticking and macromolecular leakage, while functional capillary density was effectively preserved. No differences in macro- and microhemodynamic parameters were observed between buflomedil-treated and untreated animals. These findings support the concept that activated leukocytes are involved in the microvascular manifestation of reperfusion injury and indicate that leukocyte sticking and its sequelae can be efficiently prevented by treatment with buflomedil.
Nolte
D
D
Department of Experimental Surgery, University of Heidelberg, FRG.
Lehr
H A
HA
Sack
F U
FU
Messmer
K
K
D000818:Animals; D002196:Capillaries / Q000473:pathology; D006224:Cricetinae; D003911:Dextrans; D004730:Endothelium, Vascular / Q000473:pathology; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives; D005456:Fluorescent Dyes; D007962:Leukocytes / Q000473:pathology; D008647:Mesocricetus; D008856:Microscopy, Fluorescence; D009132:Muscles / Q000098:blood supply; D011759:Pyrrolidines / Q000627:therapeutic use*; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D012867:Skin; D014665:Vasodilator Agents / Q000627:therapeutic use*
D003911:Dextrans; D005456:Fluorescent Dyes; D011759:Pyrrolidines; D014665:Vasodilator Agents; C015219:fluorescein isothiocyanate dextran; D016650:Fluorescein-5-isothiocyanate; C010651:buflomedil