Impact of dextran on microvascular disturbances and tissue injury following ischemia/reperfusion in striated muscle.
The aim of this study was to evaluate the effect of dextran (Dx) 1 versus Dx 60 (molecular weights 1,000 and 60,000) on microvascular disturbances and tissue injury in striated muscle after ischemia/reperfusion (I/R). Experiments were performed using a 4 h pressure-induced ischemia model in the hamster dorsal skinfold chamber. Three groups (n=6) of animals received a continuous infusion (45 min, 3 microL/min) of either Dx 1 or Dx 60 (total dose 5 mg/kg) or saline solution beginning 15 min before reperfusion. Intravital fluorescence microscopy allowed for quantification of functional capillary density, leukocyte adherence, extravasation of fluorescein isothiocyanate-Dx, and nonviable (propidium-positive) cell count before ischemia and .5, 2, and 24 h after reperfusion. Experiments were terminated with tissue preservation for electron microscopy. Postischemic functional capillary density was significantly improved by Dx 60 (at 24 h, 88% vs. 51% in controls). In animals receiving postischemic Dx 1 or Dx 60, leukocyte adherence was significantly reduced (at .5 h, 44% and 58%, respectively) as compared with controls, whereas macromolecular extravasation was unchanged. Nonviable cell count was significantly decreased by both Dx fractions (at 24 h, Dx 1, 75%; Dx 60, 87%), indicating a reduction of tissue injury, which was also confirmed by electron microscopy. These results provide evidence that Dx 60 at 5 mg/kg attenuates I/R injury more effectively than Dx 1. Leukocytes play a major role in the development of I/R injury, but macromolecular extravasation does not always correlate with the leukocyte-endothelium interaction and the manifestation of I/R injury.
Steinbauer
M
M
Institute for Surgical Research, University of Munich, Germany.
Harris
A G
AG
Leiderer
R
R
Abels
C
C
Messmer
K
K
D000818:Animals; D002196:Capillaries / Q000187:drug effects / Q000503:physiopathology; D002470:Cell Survival; D006224:Cricetinae; D003911:Dextrans / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000473:pathology / Q000503:physiopathology; D007511:Ischemia / Q000473:pathology / Q000503:physiopathology*; D007962:Leukocytes / Q000502:physiology; D008647:Mesocricetus; D008833:Microcirculation / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D008853:Microscopy; D008854:Microscopy, Electron; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000503:physiopathology* / Q000648:ultrastructure; D011312:Pressure; D015424:Reperfusion; D012867:Skin; D013997:Time Factors; D014699:Venules / Q000473:pathology / Q000503:physiopathology
D003911:Dextrans