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

Abstract : 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.
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Vivien Aubert, Jacques Kaminski, François Guillaud, Thierry Hauet, Patrick Hannaert. A Computer Model of Oxygen Dynamics in the Cortex of the Rat Kidney at the Cell-Tissue Level. International Journal of Molecular Sciences, MDPI, 2019, 20 (24), pp.6246. ⟨10.3390/ijms20246246⟩. ⟨hal-02988349⟩

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