Local vs. Global Blood Flow Modulation in Artificial Microvascular Networks: Effects on Red Blood Cell Distribution and Partitioning.

Alberto Mantegazza,Dominik Obrist,Matteo Ungari,Francesco Clavica

doi:10.3389/fphys.2020.566273

Alberto Mantegazza, Dominik Obrist + Show 2 more

Open Access

https://doi.org/10.3389/fphys.2020.566273

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Abstract

Our understanding of cerebral blood flow (CBF) regulation during functional activation is still limited. Alongside with the accepted role of smooth muscle cells in controlling the arteriolar diameter, a new hypothesis has been recently formulated suggesting that CBF may be modulated by capillary diameter changes mediated by pericytes. In this study, we developed in vitro microvascular network models featuring a valve enabling the dilation of a specific micro-channel. This allowed us to investigate the non-uniform red blood cell (RBC) partitioning at microvascular bifurcations (phase separation) and the hematocrit distribution at rest and for two scenarios modeling capillary and arteriolar dilation. RBC partitioning showed similar phase separation behavior during baseline and activation. Results indicated that the RBCs at diverging bifurcations generally enter the high-flow branch (classical partitioning). Inverse behavior (reverse partitioning) was observed for skewed hematocrit profiles in the parent vessel of bifurcations, especially for high RBC velocity (i.e., arteriolar activation). Moreover, results revealed that a local capillary dilation, as it may be mediated in vivo by pericytes, led to a localized increase of RBC flow and a heterogeneous hematocrit redistribution within the whole network. In case of a global increase of the blood flow, as it may be achieved by dilating an arteriole, a homogeneous increase of RBC flow was observed in the whole network and the RBCs were concentrated along preferential pathways. In conclusion, overall increase of RBC flow could be obtained by arteriolar and capillary dilation, but only capillary dilation was found to alter the perfusion locally and heterogeneously.

Highlights

Neurovascular coupling, known as functional activation or hyperemia, refers to cerebral blood flow (CBF) regulation mechanisms enabling an adequate supply of oxygen and nutrients to a localized region of the cerebral capillary network in response to increased metabolic needs (Iadecola, 2017)
Hill et al (2015) claim that even though pericytes are contractile in vivo, the cerebral blood flow is not mediated by capillaries but rather by vascular smooth muscle cells (VSMC) at the arteriolar level
Results on the hematocrit, velocity, red blood cell (RBC) flux distributions, and phase separation are presented for the honeycomb network for two different scenarios modeling a pericyte or arteriolar activation

Summary

Introduction

Neurovascular coupling, known as functional activation or hyperemia, refers to cerebral blood flow (CBF) regulation mechanisms enabling an adequate supply of oxygen and nutrients to a localized region of the cerebral capillary network in response to increased metabolic needs (Iadecola, 2017). Hall et al (2014) found that the capillary dilation upon in vivo stimulation is faster than arteriolar dilation This suggests that the neural-pericyte response is faster than the arteriolar signaling path which could play an important role in local blood flow regulation. Hill et al (2015) claim that even though pericytes are contractile in vivo, the cerebral blood flow is not mediated by capillaries but rather by VSMCs at the arteriolar level. A consensus on the spatio-temporal response of arterioles and capillary is yet to be achieved

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