Drag-Reducing Polymers Improve Vascular Hemodynamics and Tissue Oxygen Supply in Mouse Model of Diabetes Mellitus.

Abstract

Diabetes mellitus (DM) is a chronic metabolic disease characterised by hyperglycaemia and glucose intolerance caused by impaired insulin action and/or defective insulin secretion. Long-term hyperglycaemia leads to various structural and functional microvascular changes within multiple tissues, including the brain, which involves blood-brain barrier alteration, inflammation and neuronal dysfunction. We have shown previously that drag-reducing polymers (DRP) improve microcirculation and tissue oxygen supply, thereby reducing neurologic impairment in different rat models of brain injury. We hypothesised that DRP could improve cerebral and skin microcirculation in the situation of progressive microangiopathies associated with diabetes using a mouse model of diabetes mellitus. Diabetes was induced in C57BL/6 J mice with five daily consecutive intraperitoneal injections of streptozotocin (50mg/kg/day). Animals with plasma glucose concentrations greater than 250mg/dL were considered diabetic and were used in the study following four months of diabetes. DRP (2ppm) was injected biweekly during the last two weeks of the experiment. Cortical and skin (ear) microvascular cerebral blood flow (mCBF) and tissue oxygen supply (NADH) were measured by two-photon laser scanning microscopy (2PLSM). Cerebrovascular reactivity (CVR) was evaluated by measuring changes in arteriolar diameters and NADH (tissue oxygen supply) during the hypercapnia test. Transient hypercapnia was induced by a 60-second increase of CO2 concentration in the inhalation mixture from 0% to 10%. Compared to non-diabetic animals, diabetic mice had a significant reduction in the density of functioning capillaries per mm3 (787±52 vs. 449±25), the linear velocity of blood flow (1.2±0.31 vs. 0.54±0.21mm/sec), and the tissue oxygen supply (p<0.05) in both brain and skin. DRP treatment was associated with a 50% increase in all three parameters (p<0.05). According to the hypercapnia test, CVR was impaired in both diabetic groups but more preserved in DRP mice (p<0.05). Our study in a diabetic mouse model has demonstrated the efficacy of hemorheological modulation of blood flow by DRP to achieve increased microcirculatory flows and tissue oxygen supply.