Optimal occlusion uniformly partitions red blood cells fluxes within a microvascular network.
Ontology highlight
ABSTRACT:
SUBMITTER: Chang SS
PROVIDER: S-EPMC5747476 | biostudies-literature | 2017 Dec
REPOSITORIES: biostudies-literature
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.
| S-EPMC7473457 | biostudies-literature
Project description:Capillaries are the prime location for oxygen and nutrient exchange in all tissues. Despite their fundamental role, our knowledge of perfusion and flow regulation in cortical capillary beds is still limited. Here, we use in vivo measurements and blood flow simulations in anatomically accurate microvascular network to investigate the impact of red blood cells (RBCs) on microvascular flow. Based on these in vivo and in silico experiments, we show that the impact of RBCs leads to a bias toward equating the values of the outflow velocities at divergent capillary bifurcations, for which we coin the term "well-balanced bifurcations". Our simulation results further reveal that hematocrit heterogeneity is directly caused by the RBC dynamics, i.e. by their unequal partitioning at bifurcations and their effect on vessel resistance. These results provide the first in vivo evidence of the impact of RBC dynamics on the flow field in the cortical microvasculature. By structural and functional analyses of our blood flow simulations we show that capillary diameter changes locally alter flow and RBC distribution. A dilation of 10% along a vessel length of 100 ?m increases the flow on average by 21% in the dilated vessel downstream a well-balanced bifurcation. The number of RBCs rises on average by 27%. Importantly, RBC up-regulation proves to be more effective the more balanced the outflow velocities at the upstream bifurcation are. Taken together, we conclude that diameter changes at capillary level bear potential to locally change the flow field and the RBC distribution. Moreover, our results suggest that the balancing of outflow velocities contributes to the robustness of perfusion. Based on our in silico results, we anticipate that the bi-phasic nature of blood and small-scale regulations are essential for a well-adjusted oxygen and energy substrate supply.
| S-EPMC6750893 | biostudies-literature
Project description:Biomarker development is a key clinical research need in sickle cell disease (SCD). Hemorheological parameters are excellent candidates as abnormal red blood cell (RBC) rheology plays a critical role in SCD pathophysiology. Here we describe a microfluidic device capable of evaluating RBC deformability and adhesiveness concurrently, by measuring their effect on perfusion of an artificial microvascular network (AMVN) that combines microchannels small enough to require RBC deformation, and laminin (LN) coating on channel walls to model intravascular adhesion. Each AMVN device consists of three identical capillary networks, which can be coated with LN (adhesive) or left uncoated (non-adhesive) independently. The perfusion rate for sickle RBCs in the LN-coated networks (0.18 ± 0.02 nL/s) was significantly slower than in non-adhesive networks (0.20 ± 0.02 nL/s), and both were significantly slower than the perfusion rate for normal RBCs in the LN-coated networks (0.22 ± 0.01 nL/s). Importantly, there was no overlap between the ranges of perfusion rates obtained for sickle and normal RBC samples in the LN-coated networks. Interestingly, treatment with poloxamer 188 decreased the perfusion rate for sickle RBCs in LN-coated networks in a dose-dependent manner, contrary to previous studies with conventional assays, but in agreement with the latest clinical trial which showed no clinical benefit. Overall, these findings suggest the potential utility of the adhesive AMVN device for evaluating the effect of novel curative and palliative therapies on the hemorheological status of SCD patients during clinical trials and in post-market clinical practice.
| S-EPMC8113687 | biostudies-literature
Project description:Plasmodium falciparum malaria parasites within human red blood cells (RBCs) have been successfully transfected to produce chloramphenicol acetyltransferase (CAT). Electroporation of parasitized RBCs was used to introduce plasmids that have CAT-encoding DNA flanked by 5' and 3' untranslated sequences of the P. falciparum hsp86, hrp3, and hrp2 genes. These flanking sequences were required for expression as their excision abolished CAT activity in transfected parasites. Transfection signals from native CAT-encoding DNA compared well with those from a synthetic DNA sequence adapted to the P. falciparum major codon bias, demonstrating effective expression of the bacterial sequence despite its use of rare P. falciparum codons. Transfected ring-stage parasites produced CAT signals at least as strong as transfected schizont-stage parasites even though ring stages are surrounded by more RBC cytoplasm than schizonts. The transfection of erythrocyte-stage P. falciparum parasites advances our ability to pursue genetic analysis of this major pathogen.
| S-EPMC42619 | biostudies-other
Project description:BackgroundRed blood cell (RBC) transfusion is a common treatment for hospitalized patients. However, the effects of RBC transfusion on microvascular function remain controversial.MethodsIn a medical ICU in a tertiary teaching hospital, we prospectively included anemic patients requiring RBC transfusion. Skin microvascular reactivity was measured before and 30?min after RBC transfusion. Plasma was collected to analyze intravascular hemolysis and draw the lipidomic and cytokine profiles.ResultsIn a cohort of 59 patients, the median age was 66 [55-81] years and SAPS II was 38 [24-48]. After RBC transfusion, endothelium-dependent microvascular reactivity improved in 35 (59%) patients, but worsened in 24 others (41%). Comparing clinical and biological markers revealed that baseline blood leucokyte counts distinguished improving from worsening patients (10.3 [5.7; 19.7] vs. 4.6 [2.1; 7.3] ×?109/L; p?=?0.001) and correlated with variations of microvascular reactivity (r?=?0.36, p?=?0.005). Blood platelet count was also higher in improving patients (200 [97; 280] vs 160 [40; 199] ×?103/mL, p?=?0.03) but did not correlate with variations of microvascular reactivity. We observed no intravascular hemolysis (HbCO, heme, bilirubin, LDH), but recorded a significant increase in RBC microparticle levels specific to improving patients after transfusion (292 [108; 531] vs. 53 [34; 99] MP/?L; p?=?0.03). The improvement in microvascular dilation was positively correlated with RBC microparticle levels (R?=?0.83, p?<?0.001) and conversion of arachidonic acid into vasodilating eicosanoids.ConclusionsPatients displaying an improved microvascular reactivity after RBC transfusion had high blood leukocyte counts, increased RBC microparticle formation, and enhanced metabolism of arachidonic acid into vasodilating lipids. Our data suggested a contribution of recipient leukocytes to the vascular impact of RBC transfusion.
| S-EPMC6717366 | biostudies-literature
Project description: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.
| S-EPMC7571285 | biostudies-literature
Project description:Background This study aimed to investigate longitudinal physiological changes in the recanalized coronary chronic total occlusion (CTO) vessel and its dependent myocardium after successful percutaneous coronary intervention (PCI). Methods and Results In this pilot study, 25 patients scheduled for elective CTO PCI with viable myocardium and angiographically visible collaterals were included. Absolute coronary blood flow and absolute microvascular resistance were measured invasively using continuous thermodilution. Measurements were performed immediately after successful CTO PCI and at short-term follow-up. In a subgroup of patients, physiological measurements were performed at the predominant donor vessel before CTO PCI, immediately afterwards, and at follow-up. Absolute coronary blood flow in the recanalized CTO artery increased from 148±53 mL/min immediately after PCI to 221±77 mL/min at follow-up (P<0.001). In agreement, absolute resistance in the myocardial territory perfused by the CTO artery, decreased from 545±255 Wood units immediately after the procedure to 387±128 Wood units at follow-up (P=0.014). There were no significant changes in the absolute coronary blood flow and resistance in the predominant donor between baseline and follow-up. Positive remodeling of the distal CTO vessel with an increase in lumen diameter was observed. Conclusions After successful CTO PCI, blood flow in the recanalized artery and microvascular function of the dependent myocardium are not immediately normal but recover over time.
| S-EPMC7428549 | biostudies-literature
Project description:Damage to the blood vessel triggers formation of a hemostatic plug, which is meant to prevent bleeding, yet the same phenomenon may result in a total blockade of a blood vessel by a thrombus, causing severe medical conditions. Here, we show that the physical interplay between platelet adhesion and hemodynamics in a microchannel manifests in a critical threshold behavior of a growing thrombus. Depending on the size of injury, two distinct dynamic pathways of thrombosis were found: the formation of a nonocclusive plug, if injury length does not exceed the critical value, and the total occlusion of the vessel by the thrombus otherwise. We develop a mathematical model that demonstrates that switching between these regimes occurs as a result of a saddle-node bifurcation. Our study reveals the mechanism of self-regulation of thrombosis in blood microvessels and explains experimentally observed distinctions between thrombi of different physical etiology. This also can be useful for the design of platelet-aggregation-inspired engineering solutions.
| S-EPMC4621855 | biostudies-literature
Project description:Clinically, red blood cell abnormalities are closely related to tumor diseases, red blood cell diseases, internal medicine, and other diseases. Red blood cell classification is the key to detecting red blood cell abnormalities. Traditional red blood cell classification is done manually by doctors, which requires a lot of manpower produces subjective results. This paper proposes an Attention-based Residual Feature Pyramid Network (ARFPN) to classify 14 types of red blood cells to assist the diagnosis of related diseases. The model performs classification directly on the entire red blood cell image. Meanwhile, a spatial attention mechanism and channel attention mechanism are combined with residual units to improve the expression of category-related features and achieve accurate extraction of features. Besides, the RoI align method is used to reduce the loss of spatial symmetry and improve classification accuracy. Five hundred and eighty eight red blood cell images are used to train and verify the effectiveness of the proposed method. The Channel Attention Residual Feature Pyramid Network (C-ARFPN) model achieves an mAP of 86%; the Channel and Spatial Attention Residual Feature Pyramid Network (CS-ARFPN) model achieves an mAP of 86.9%. The experimental results indicate that our method can classify more red blood cell types and better adapt to the needs of doctors, thus reducing the doctor's time and improving the diagnosis efficiency.
| S-EPMC8712440 | biostudies-literature
Project description:A key concept in nanomedicine is encapsulating therapeutic or diagnostic agents inside nanoparticles to prolong blood circulation time and to enhance interactions with targeted cells. During circulation and depending on the selected application (e.g., cancer drug delivery or immune modulators), nanoparticles are required to possess low or high interactions with cells in human blood and blood vessels to minimize side effects or maximize delivery efficiency. However, analysis of cellular interactions in blood vessels is challenging and is not yet realized due to the diverse components of human blood and hemodynamic flow in blood vessels. Here, the first comprehensive method to analyze cellular interactions of both synthetic and commercially available nanoparticles under human blood flow conditions in a microvascular network is developed. Importantly, this method allows to unravel the complex interplay of size, charge, and type of nanoparticles on their cellular associations under the dynamic flow of human blood. This method offers a unique platform to study complex interactions of any type of nanoparticles in human blood flow conditions and serves as a useful guideline for the rational design of liposomes and polymer nanoparticles for diverse applications in nanomedicine.
| S-EPMC7361276 | biostudies-literature