Skeletal muscle microcirculatory structure and hemodynamics in diabetes

Abstract

Within skeletal muscle, insulin-dependent (Type 1) diabetes produces straighter, narrower capillaries. To test the hypothesis that these microvascular alterations would be associated with impaired capillary hemodynamics, intravital microscopy techniques were used to study the in vivo spinotrapezius muscle microcirculation of age-matched control (C) and streptozotocin (STZ) induced diabetic (D) rats. D rats exhibited a marked reduction in body weight (C, 266±5 g; D, 150±6 g; P<0.001). At resting sarcomere lengths (i.e. ≈2.7 μm), the additional capillary length arising from tortuosity and branching was less in D muscle (C, 10.5±0.8%; D, 5.3±1.0%, P<0.01). Capillary diameter was reduced in D muscle (C, 5.4±0.1 μm; D, 4.6±0.1 μm; P<0.001), and was positively correlated ( r=0.71) with the decreased proportion of capillaries sustaining flow (C, 85±5%; D, 53±3%; P<0.001). Within those ‘flowing’ capillaries, red blood cell (RBC) velocity and flux were reduced 29 and 43%, respectively in D muscle (both P<0.05). This reduced calculated O 2 delivery by 57% per unit tissue width and 41% per unit muscle mass. Capillary ‘tube’ hematocrit was unchanged from control values (C, 0.22±0.02; D, 0.22±0.02). We conclude that, in the diabetic state, microvascular remodeling is associated with a reduced proportion of ‘flowing’ capillaries and a reduction in RBC velocity and flux in these vessels such that skeletal muscle O 2 delivery is markedly reduced.