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      Dynamic Changes in Microvascular Flow Conductivity and Perfusion After Myocardial Infarction Shown by Image‐Based Modeling

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          Abstract

          Background

          Microcirculation is a decisive factor in tissue reperfusion inadequacy following myocardial infarction ( MI). Nonetheless, experimental assessment of blood flow in microcirculation remains a bottleneck. We sought to model blood flow properties in coronary microcirculation at different time points after MI and to compare them with healthy conditions to obtain insights into alterations in cardiac tissue perfusion.

          Methods and Results

          We developed an image‐based modeling framework that permitted feeding a continuum flow model with anatomical data previously obtained from the pig coronary microvasculature to calculate physiologically meaningful permeability tensors. The tensors encompassed the microvascular conductivity and were also used to estimate the arteriole–venule drop in pressure and myocardial blood flow. Our results indicate that the tensors increased in a bimodal pattern at infarcted areas on days 1 and 7 after MI while a nonphysiological decrease in arteriole–venule drop in pressure was observed; contrary, the tensors and the arteriole–venule drop in pressure on day 3 after MI, and in remote areas, were closer to values for healthy tissue. Myocardial blood flow calculated using the condition‐dependent arteriole–venule drop in pressure decreased in infarcted areas. Last, we simulated specific modes of vascular remodeling, such as vasodilation, vasoconstriction, or pruning, and quantified their distinct impact on microvascular conductivity.

          Conclusions

          Our study unravels time‐ and region‐dependent alterations of tissue perfusion related to the structural changes occurring in the coronary microvasculature due to MI. It also paves the way for conducting simulations in new therapeutic interventions in MI and for image‐based microvascular modeling by applying continuum flow models in other biomedical scenarios.

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          Most cited references37

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          Microcirculation and Hemorheology.

          Major experimental and theoretical studies on microcirculation and hemorheology are reviewed with the focus on mechanics of blood flow and the vascular wall. Flow of the blood formed elements (red blood cells (RBCs), white blood cells or leukocytes (WBCs) and platelets) in individual arterioles, capillaries and venules, and in microvascular networks is discussed. Mechanical and rheological properties of the formed elements and their interactions with the vascular wall are reviewed. Short-term and long-term regulation of the microvasculature is discussed; the modes of regulation include metabolic, myogenic and shear-stress-dependent mechanisms as well as vascular adaptation such as angiogenesis and vascular remodeling.
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            Blood flow in microvascular networks. Experiments and simulation.

            A theoretical model has been developed to simulate blood flow through large microcirculatory networks. The model takes into account the dependence of apparent viscosity of blood on vessel diameter and hematocrit (the Fahraeus-Lindqvist effect), the reduction of intravascular hematocrit relative to the inflow hematocrit of a vessel (the Fahraeus effect), and the disproportionate distribution of red blood cells and plasma at arteriolar bifurcations (phase separation). The model was used to simulate flow in three microvascular networks in the rat mesentery with 436,583, and 913 vessel segments, respectively, using experimental data (length, diameter, and topological organization) obtained from the same networks. Measurements of hematocrit and flow direction in all vessel segments of these networks tested the validity of model results. These tests demonstrate that the prediction of parameters for individual vessel segments in large networks exhibits a high degree of uncertainty; for example, the squared coefficient of correlation between predicted and measured hematocrit of single vessel segments ranges only between 0.15 and 0.33. In contrast, the simulation of integrated characteristics of the network hemodynamics, such as the mean segment hematocrit or the distribution of blood flow velocities, is very precise. In addition, the following conclusions were derived from the comparison of predicted and measured values: 1) The low capillary hematocrits found in mesenteric microcirculatory networks as well as their heterogeneity can be explained on the basis of the Fahraeus effect and phase-separation phenomena. 2) The apparent viscosity of blood in vessels of the investigated tissue with diameters less than 15 microns is substantially higher than expected compared with measurements in glass tubes with the same diameter.
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              Blood Flow in the Microcirculation

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                Author and article information

                Contributors
                agarroyo@cib.csic.es
                Journal
                J Am Heart Assoc
                J Am Heart Assoc
                10.1002/(ISSN)2047-9980
                JAH3
                ahaoa
                Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
                John Wiley and Sons Inc. (Hoboken )
                2047-9980
                22 March 2019
                02 April 2019
                : 8
                : 7 ( doiID: 10.1002/jah3.2019.8.issue-7 )
                : e011058
                Affiliations
                [ 1 ] Centro Nacional de Investigaciones Cardiovasculares (CNIC) Madrid Spain
                [ 2 ] Biomedical Image Technologies (BIT), ETSI Telecomunicación, Universidad Politécnica de Madrid Madrid Spain
                [ 3 ] Institute of Biomedical Engineering Department of Engineering Science University of Oxford United Kingdom
                [ 4 ] Division of Science, Mathematics, and Computing Bard College Annandale‐on‐Hudson NY
                [ 5 ] Centro de Investigación Biomédica en Red de Bioingeniería Biomateriales y Nanomedicina (CIBERBBN) Madrid Spain
                [ 6 ] Department of Biomedical Engineering School of Medicine Johns Hopkins University Baltimore MD
                [ 7 ] Centro de Investigaciones Biológicas (CIB‐CSIC) Madrid Spain
                Author notes
                [*] [* ] Correspondence to: Alicia G. Arroyo, MD, PhD, Centro de Investigaciones Biológicas (CIB‐CSIC), Ramiro de Maeztu, 9, 28040 Madrid, Spain. E‐mail: agarroyo@ 123456cib.csic.es
                Article
                JAH33982
                10.1161/JAHA.118.011058
                6509718
                30897998
                a7898dd6-8170-48e4-9a45-0c44afa69e3f
                © 2019 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 25 September 2018
                : 19 February 2019
                Page count
                Figures: 6, Tables: 4, Pages: 31, Words: 12797
                Funding
                Funded by: European Union's Seventh Framework Programme
                Award ID: FP7/2007–2013
                Award ID: 608027
                Funded by: Spanish Ministerio de Ciencia, Innovación y Universidades
                Award ID: SAF2017‐83229‐R
                Award ID: TEC2015‐66978‐R
                Funded by: NIH
                Award ID: R01HL101200
                Funded by: Doctoral Training Partnership
                Award ID: EP/M50659X/1
                Categories
                Original Research
                Original Research
                Coronary Heart Disease
                Custom metadata
                2.0
                jah33982
                April 2019
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.6.2.1 mode:remove_FC converted:02.04.2019

                Cardiovascular Medicine
                blood flow,confocal microscopy,coronary microcirculation,mathematical modeling,myocardial infarction,computational biology,hemodynamics,ischemia,myocardial biology

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