Acute hyperglycaemia causes severe disturbances of mesenteric microcirculation in an in vivo rat model

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Abstract

Background

Chronic hyperglycaemia in diabetes is suggested to be a major cause of diabetic angiopathy. Up until now, the effects of acutely induced hyperglycaemia in non-diabetic subjects as well as hyperglycaemic effects in early diabetes, on mesenteric microcirculation and leucocyte endothelial cell interaction have not been investigated extensively.

Methods

The aim of this study was to examine rat mesenteric microcirculatory parameters such as leucocyte adhesion, leucocyte emigration, venular shear rate and leucocyte rolling velocity using a new rat model both with continuous venous glucose infusion and with continuous arterial measurement of blood glucose concentration while observing mesenteric microcirculation with in vivo capillary microscopy in the non-diabetic and diabetic state.

Results

In normal non-diabetic rats, acute elevation of glucose concentration resulted in a highly significant, rapid and step-by-step enhancement of adhesion and emigration in a dose dependent manner. Leucocyte rolling velocity was reduced with rising glucose levels. Venular shear rate showed a similar reduction at all hyperglycaemic levels. In streptozotocin-induced diabetes, adhesion and emigration were significantly enhanced while shear rate and leucocyte rolling velocity were severely reduced, resembling the effects of glucose infusion experiments. Longer duration of diabetes resulted in a further enhancement of leucocyte adhesion and reduction of leucocyte rolling velocity while emigration and shear rate were not influenced by a longer period of diabetes manifestation.

Conclusion

Experiments using different mannitol concentrations revealed that most of the observed glucose effects can be mimicked by mannitol and are therefore - at least in part - due to changes in osmolarity by yet unknown mechanisms.

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