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1 Department of Anesthesiology, Academic Medical Center, Amsterdam, The Netherlands
2 Department of Biology, University of Istanbul, Istanbul, Turkey
3 Department of Physiology, Academic Medical Center, Amsterdam, The Netherlands
4 Department of Medical Physics, Academic Medical Center, Amsterdam, The Netherlands
* To whom correspondence should be addressed. E-mail: c.j.zuurbier{at}amc.uva.nl.
Hyperglycemia is becoming recognized as an important risk factor for microvascular dysfunction. We hypothesized that short-term hyperglycemia, either on the scale of hours or weeks, alters the barrier function and the volume of the endothelial glycocalyx and decreases functional capillary density and deformability of the red blood cells. All experiments were performed in anesthetized, mechanically ventilated, C57Bl6 mice, that were either normoglycemic, acutely hyperglycemic (25 mM) for 60 min due to infusion of glucose, or hyperglycemic (25 mM) for 2-4 weeks (db/db mice). The glycocalyx was probed using 40-kDa Texas Red dextran, which is known to permeate the glycocalyx, and 70-kDa FITC dextran which has impaired access to the glycocalyx in healthy animals. Clearance of the dye from the blood was measured. An orthogonal polarization spectral imaging technique was used to visualize the number of capillaries with flowing RBC's of the dorsal flexor muscle. The data indicate that short-term hyperglycemia causes a rapid decrease of the ability of the glycocalyx to exclude 70-kDa dextran. No change in the vascular permeation of 40-kDa dextran was observed. Glycocalyx volume was not affected by short-term hyperglycemia. In addition, 1 hour of hyperglycemia resulted in a 38% decrease of the lineal density of capillaries with flowing RBCs. This decreased lineal density was not observed in the 2-4 week hyperglycemia model. Short-term hyperglycemia was without any effect on the deformablity of the red blood cells. The date indicate that the described increased vascular permeability with hyperglycemia can be ascribed to an increased permeability of the glycocalyx, identifying the glycocalyx as a potential early target of hyperglycemia.
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