Insights on Microvascular Flow Regulation in Microvascular Units: A Computational Modeling Study

Abstract

BackgroundRegulation of RBC oxygen delivery and plasma flow is a critical function of the microcirculation. Given the complexity of microvascular networks, mathematical modeling has been an essential adjunct for understanding physiological principles. Many studies have simulated flow through branching arteriolar networks or isolated groups of capillaries, but the completed microvascular units (MVU) ‐ from terminal arteriole, through a capillary bundle, and into a post‐capillary venule ‐ has rarely been studied. Modeling this fundamental microvascular structure will help describe how capillary networks interface with the broader microcirculation and provide insight into properties of flow regulation on this scale.MethodsWe constructed an idealized MVU and applied a dual‐phase steady‐state blood flow model to solve for RBC and plasma flow. We incorporated physiologic parameters that were varied individually while keeping all of the other variables constant: (i) number of parallel capillaries in a bundle (4–10 capillaries), (ii) capillary length (50–600 micron), (iii) arteriolar inflow hematocrit (0.1–0.5), (iv) arteriolar diameter (6–18 micron), (v) venular diameter (6–18 micron), and (vi) driving pressure across the MVU. Mean and coefficient of variation (CV) were calculated for RBC flow, plasma flow, and tube hematocrit (HT) for all parallel capillaries.ResultsPlasma flow is significantly more variable than RBC flow in capillaries for all test cases in this study. Increasing the number of capillaries per bundle decreased the mean RBC and plasma flow but increased total flow through the MVU; plasma flow CV (17%–54%) and HT CV (19%–52%) increased substantially while RBC flow CV was much less affected (4%–9%). Increasing capillary length reduced mean RBC flow, plasma flow, and HT nonlinearly with an inflection point occurring at capillary lengths of 200 microns or greater. Increasing arteriolar inflow hematocrit reduced RBC flow CV (16% vs 2%) and increased plasma flow CV (26%–36%). Increases to arteriolar and venular diameter above 10 microns had little effect on the magnitude or distribution of RBC and plasma flow through the MVU. Changes to the driving pressure across the MVU had a linear effect on RBC and plasma flow with no effect on the relative distribution between capillaries.ConclusionsThis study provides insight into how the biophysical properties of the microcirculation may influence flow regulation through completed microvascular units. Pre‐ and post‐capillary microvessels appear optimized for diameters less than 10 microns. Modifications to driving pressure provide a much more straight forward method of flow regulation than alterations to vessel diameter. Future work will compare these results against in vivo capillary measurements with heterogeneous spatial geometry and explore modeling approaches for multiple interconnected MVU. Example of one idealized microvascular unit included in the study; this microvascular unit has 6 parallel capillaries with length 300 microns.imageExample of one idealized microvascular unit included in the study; this microvascular unit has 6 parallel capillaries with length 300 microns.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.