Dataset Information

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

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.

SUBMITTER: Mantegazza A

PROVIDER: S-EPMC7571285 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Mantegazza Alberto A Ungari Matteo M Clavica Francesco F Obrist Dominik D

Frontiers in physiology 20200925

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 <i>in vitro</i> microvascular network models featuring a valve enabling the dilation of a specific micro-channel. This allowed us to in ...[more]

PMID: 33123027

Similar Datasets

Project description:Abnormal red blood cell (RBC) deformability contributes to hemolysis, thrombophilia, inflammation, and microvascular occlusion in various circulatory diseases. A quantitative and objective assessment of microvascular occlusion mediated by RBCs with abnormal deformability would provide valuable insights into disease pathogenesis and therapeutic strategies. To that end, we present a new functional microfluidic assay, OcclusionChip, which mimics two key architectural features of the capillary bed in the circulatory system. First, the embedded micropillar arrays within the microchannel form gradient microcapillaries, from 20 μm down to 4 μm, which mimic microcapillary networks. These precisely engineered microcapillaries retain RBCs with impaired deformability, such that stiffer RBCs occlude the wider upstream microcapillaries, while less stiff RBCs occlude the finer downstream microcapillaries. Second, the micropillar arrays are coupled with two side passageways, which mimic the arteriovenous anastomoses that act as shunts in the capillary bed. These side microfluidic anastomoses prevent microchannel blockage, and enable versatility and testing of clinical blood samples at near-physiologic hematocrit levels. Further, we define a new generalizable parameter, Occlusion Index (OI), which is an indicative index of RBC deformability and the associated microcapillary occlusion. We demonstrate the promise of OcclusionChip in diverse pathophysiological scenarios that result in impaired RBC deformability, including mercury toxin, storage lesion, end-stage renal disease, malaria, and sickle cell disease (SCD). Hydroxyurea therapy improves RBC deformability and increases fetal hemoglobin (HbF%) in some, but not all, treated patients with SCD. HbF% greater than 8.6% has been shown to improve clinical outcomes in SCD. We show that OI associates with HbF% in 16 subjects with SCD. Subjects with higher HbF levels (HbF > 8.6%) displayed significantly lower OI (0.88% ± 0.10%, N = 6) compared with those with lower HbF levels (HbF ≤ 8.6%) who displayed greater OI (3.18% ± 0.34%, N = 10, p < 0.001). Moreover, hypoxic OcclusionChip assay revealed a significant correlation between hypoxic OI and subject-specific sickle hemoglobin (HbS) level in SCD. OcclusionChip enables versatile in vitro assessment of microvascular occlusion mediated by RBCs in a wide range of clinical conditions. OI may serve as a new parameter to evaluate the efficacy of treatments improving RBC deformability, including hemoglobin modifying drugs, anti-sickling agents, and genetic therapies.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets