A streak length-based method for quantifying red blood cell flow in skeletal muscle arteriolar networks.

OBJECTIVE: To develop an experimental method to quantify RBC flow throughout skeletal muscle arteriolar networks. METHODS: Data on arteriolar geometry were obtained using IVVM of the rat GM. RBC velocities and number densities were also obtained during these experiments using fluorescently labeled RBCs. Arteriolar and RBC data were combined to estimate blood volume flow rates, HT and HD values, and RBC volume flow rates. Validation of hematocrit and RBC flow results was performed at arteriolar bifurcations using both mass balance and comparisons to an established model of the PS effect. RESULTS: Estimated HT values were within the expected range (6%-34%) for the arterioles considered (29-130 µm). RBC mass balance error was 18 ± 16% (mean ± SD, n = 7 bifurcations). RBC outflow from diverging bifurcations as a function of RBC inflow was given by Y = 0.986*X + 0.331 with R2  = 0.987. Outflow HT as a function of the PS prediction was given by Y = 1.034*X + 0.004 with R2  = 0.691. RBC outflow as a function of the prediction was given by Y = 0.917*X + 0.804 with R2  = 0.891. CONCLUSIONS: An experimental method has been developed and validated that can easily and accurately quantify RBC flow distribution in large skeletal muscle arteriolar networks and provides direct estimates of HT values.

Estimating blood flow in skeletal muscle arteriolar trees reconstructed from in vivo data using the Fry approach.

OBJECTIVE: To develop a computational method to accurately predict blood flow in skeletal muscle arteriolar trees in the absence of complete boundary data. METHODS: We used arteriolar trees in the rat GM muscle that were reconstructed from montages obtained via IVVM, and incorporated a recently published method for approximating unknown b.c.'s into our existing two-phase, steady-state blood flow model. For varying numbers of unknown b.c.'s, we used the new flow model and GM geometry to approximately match RBC flows corresponding to experimental measurements. RESULTS: We showed this method gives errors that decrease as the number of unknown b.c.'s decreases. We also showed that specifying total blood flow decreases the mean RBC flow error and its variability. By varying required target values of intravascular pressure and wall shear stress, we showed results are less sensitive to target pressure. Finally, we developed and validated a method for determining target values, so that network hemodynamics and resistance can be accurately calculated based only on measured or estimated total blood flow. CONCLUSIONS: We have developed and validated a computational method that can accurately estimate RBC flow distribution in skeletal muscle arteriolar trees in the absence of complete boundary data.

Altered post-capillary and collecting venular reactivity in skeletal muscle with metabolic syndrome.

KEY POINTS: With the development of the metabolic syndrome, both post-capillary and collecting venular dilator reactivity within the skeletal muscle of obese Zucker rats (OZR) is impaired. The impaired dilator reactivity in OZR reflects a loss in venular nitric oxide and PGI2 bioavailability, associated with the chronic elevation in oxidant stress. Additionally, with the impaired dilator responses, a modest increase in adrenergic constriction combined with an elevated thromboxane A2 production may contribute to impaired functional dilator and hyperaemic responses at the venular level. For the shift in skeletal muscle venular function with development of the metabolic syndrome, issues such as aggregate microvascular perfusion resistance, mass transport and exchange within with capillary networks, and fluid handling across the microcirculation are compelling avenues for future investigation. ABSTRACT: While research into vascular outcomes of the metabolic syndrome has focused on arterial/arteriolar and capillary levels, investigation into venular function and how this impacts responses has received little attention. Using the in situ cremaster muscle of obese Zucker rats (OZR; with lean Zucker rats (LZR) as controls), we determined indices of venular function. At ∼17 weeks of age, skeletal muscle post-capillary venular density was reduced by ∼20% in LZR vs. OZR, although there was no evidence of remodelling of the venular wall. Venular tone at ∼25 µm (post-capillary) and ∼75 µm (collecting) diameter was elevated in OZR vs. LZR. Venular dilatation to acetylcholine was blunted in OZR vs. LZR due to increased oxidant stress-based loss of nitric oxide bioavailability (post-capillary) and increased α1 - (and α2 -) mediated constrictor tone (collecting). Venular constrictor responses in OZR were comparable to LZR for most stimuli, although constriction to α1 -adrenoreceptor stimulation was elevated. In response to field stimulation of the cremaster muscle (0.5, 1, 3 Hz), venular dilator and hyperaemic responses to lower frequencies were blunted in OZR, but responses at 3 Hz were similar between strains. Venous production of TxA2 was higher in OZR than LZR and significantly higher than PGI2 production in either following arachidonic acid challenge. These results suggest that multi-faceted alterations to skeletal muscle venular function in OZR may contribute to alterations in upstream capillary pressure profiles and the transcapillary exchange of solutes and water under conditions of metabolic syndrome.