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 ver sus Dx 60 (molecular weights 1,000 and 60,000) on microvascular distur bances and tissue injury in striated muscle after ischemia/reperfusion (I/R). Experiments were performed using a 4 h pressure-induced ischem ia model in the hamster dorsal skinfold chamber. Three groups (n = 6) of animals received a continuous infusion (45 min, 3 mu L/min) of eith er 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 (propidi um-positive) cell count before ischemia and .5, 2, and 24 h after repe rfusion. Experiments were terminated with tissue preservation for elec tron microscopy. Postischemic functional capillary density was signifi cantly improved by Dx 60 (at 24 h, 88% vs. 51% in controls). In animal s receiving postischemic Dx 1 or Dx 60, leukocyte adherence was signif icantly reduced (at .5 h, 44% and 58%, respectively) as compared with controls, whereas macromolecular extravasation was unchanged. Nonviabl e cell count was significantly decreased by both Dx fractions (at 24 h , Dx 1, 75%; Dx 60, 87%), indicating a reduction of tissue injury, whi ch was also confirmed by electron microscopy. These results provide ev idence that Dx 60 at 5 mg/kg attenuates I/R injury more effectively th an 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.