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

Background Chronic hyperglycaemia in diabetes is suggested to be a major ca use of diabetic angiopathy. Up until now, the effects of acutely induced hy perglycaemia in nondiabetic subjects as well as hyperglycaemic effects in e arly diabetes, on mesenteric microcirculation and leucocyte endothelial cel l interaction have not been investigated extensively. Methods The aim of this study was to examine rat mesenteric microcirculator y parameters such as leucocyte adhesion, leucocyte emigration, venular shea r rate and leucocyte rolling velocity using a new rat model both with conti nuous Venous glucose infusion and with continuous arterial measurement of b lood glucose concentration while observing mesenteric microcirculation with in vine capillary microscopy in the non-diabetic and diabetic state. Results In normal non-diabetic rats, acute elevation of glucose concentrati on resulted in a highly significant, rapid and step-by- step enhancement of adhesion and emigration in a dose dependent manner. Leucocyte rolling velo city was reduced with rising glucose levels. Venular shear rate showed a si milar reduction at all hyperglycaemic levels. In streptozotocin-induced dia betes, adhesion and emigration were significantly enhanced while shear rate and leucocyte rolling velocity were severely reduced, resembling the effec ts of glucose infusion experiments. Longer duration of diabetes resulted in a further enhancement of leucocyte adhesion and reduction of leucocyte rol ling velocity while emigration and shear rate were not influenced by a long er period of diabetes manifestation. Conclusion Experiments using different mannitol concentrations revealed tha t 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 me chanisms.