Effects Of Type II Diabetes On Capillary Hemodynamics In Skeletal Muscle

Abstract

PURPOSE A decreased microvascular driving pressure for O2 (PO2m) has been implicated in the slowed VO2 kinetics and exercise intolerance found in Type II diabetic patients (Padilla et al., The Physiologist, 47:351(A35.3), 2004). In accordance with Fick's Law (VO2=D(PO2m)), alterations in diffusing capacity for O2 (i.e. D) at any given PO2m play a deterministic role in blood-muscle O2 flux (i.e. VO2). Given the above, we hypothesized that Type II diabetes will reduce the diffusing capacity for O2, and thus O2 flux, by impairing capillary hemodynamics within the muscle microcirculation of the Goto-Kakizaki Type II diabetic rat (Dia). METHODS Using intravital microscopy, we measured capillary diameter, capillary lineal density, hematocrit (Hcttube), and red blood cell flux (Frbc) and velocity (Vrbc) in the spinotrapezius muscle of healthy Wistar (Con: n=5; bwt: 553±18 g; fasting blood glucose: 105±5 mg/dl) and Dia (n=7, bwt = 417±14, fasting blood glucose: 263±34 mg/dl; both P<0.05 vs. Con) rats under resting conditions. RESULTS Mean arterial pressure did not differ between groups (Con: 117±6; Dia: 110±10 mmHg; P>0.05), but heart rate was elevated in the Dia rats (Con: 371±13; Dia: 437±14 beats/min; P<0.05). Sarcomere length was set (Con: 2.0±0.1; Dia: 2.1±0.1 μm; P >0.05) to ensure that muscle stretching did not alter capillary hemodynamics. Capillary diameter was not different (Con: 4.7±0.1; Dia: 5.1±0.2 μm; P>0.05), but Hcttube was higher in Con vs. Dia rats (Con: 33±0.1; Dia: 23±0.1 %: P<0.05). Additionally, the percentage of RBC-perfused capillaries (Con: 92±4; Dia: 60±6 %), Vrbc (Con: 514±18, Dia: 179±40 μm/s), and Frbc (Con: 47±3; Dia: 16±5 RBC/s) were all decreased in Dia (all P<0.05). Consequently, O2 delivery per unit of muscle was lower in the Dia vs. Con (Con: 983±112, Dia: 295±58 RBC/s/mm muscle; P<0.05). CONCLUSION The results of this study indicate that Type II diabetes reduces both the convective O2 delivery and diffusive O2 transport properties of skeletal muscle at rest. In turn, this may affect O2 availability, delivery, and exchange during the onset of exercise thus contributing to the slowed VO2 kinetics and greater utilization of anaerobic energy sources exhibited by Type II diabetic patients. Supported by HL-69739, HL-67619, HL-50306, and AG-19228.