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A Computer Model of Oxygen Dynamics in the Cortex of the Rat Kidney at the Cell-Tissue Level

Title: A Computer Model of Oxygen Dynamics in the Cortex of the Rat Kidney at the Cell-Tissue Level
Authors: Aubert, Vivien; Kaminski, Jacques; Guillaud, François; Hauet, Thierry; Hannaert, Patrick
Contributors: Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques U 1082 (IRTOMIT Poitiers ); Université de Poitiers = University of Poitiers (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Source: ISSN: 1661-6596.
Publisher Information: CCSD; MDPI
Publication Year: 2019
Collection: Université de Poitiers: Publications de nos chercheurs.ses (HAL)
Subject Terms: oxygen consumption; Na reabsorption; agent-based model; hemoglobin; rat; proximal tubule; peritubular capillary; renal cortex; oxygen; kidney; [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences; [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM]; [SDV.IB]Life Sciences [q-bio]/Bioengineering
Description: International audience ; The renal cortex drives renal function. Hypoxia/reoxygenation are primary factors in ischemia-reperfusion (IR) injuries, but renal oxygenation per se is complex and awaits full elucidation. Few mathematical models address this issue: none captures cortical tissue heterogeneity. Using agent-based modeling, we develop the first model of cortical oxygenation at the cell-tissue level (RCM), based on first principles and careful bibliographical analysis. Entirely parameterized with Rat data, RCM is a morphometrically equivalent 2D-slice of cortical tissue, featuring peritubular capillaries (PTC), tubules and interstitium. It implements hemoglobin/O 2 binding-release, oxygen diffusion, and consumption, as well as capillary and tubular flows. Inputs are renal blood flow RBF and PO 2 feeds; output is average tissue PO 2 (tPO 2). After verification and sensitivity analysis, RCM was validated at steady-state (tPO 2 37.7 ± 2.2 vs. 36.9 ± 6 mmHg) and under transients (ischemic oxygen half-time: 4.5 ± 2.5 vs. 2.3 ± 0.5 s in situ). Simulations confirm that PO 2 is largely independent of RBF, except at low values. They suggest that, at least in the proximal tubule, the luminal flow dominantly contributes to oxygen delivery, while the contribution of capillaries increases under partial ischemia. Before addressing IR-induced injuries, upcoming developments include ATP production, adaptation to minutes-hours scale, and segmental and regional specification.
Document Type: article in journal/newspaper
Language: English
DOI: 10.3390/ijms20246246
Availability: https://cnrs.hal.science/hal-02988349; https://cnrs.hal.science/hal-02988349v1/document; https://cnrs.hal.science/hal-02988349v1/file/AUBERT-ijms-20-06246.pdf; https://doi.org/10.3390/ijms20246246
Rights: http://creativecommons.org/licenses/by/ ; info:eu-repo/semantics/OpenAccess
Accession Number: edsbas.663BAB03
Database: BASE