Title

Mathematical Model of Oxygen Transport in Tuberculosis Granulomas

Publication Date

2015

Journal

Annals of Biomedical Engineering

Volume

44

Issue

4

First Page

863

Last Page

872

Department

Biomedical Engineering

Abstract

Pulmonary granulomas—the hallmark of Mycobacterium tuberculosis (MTB) infection—are dense cellular lesions that often feature regions of hypoxia and necrosis, partially due to limited transport of oxygen. Low oxygen in granulomas can impair the host immune response, while MTB are able to adapt and persist in hypoxic environments. Here, we used a physiologically based mathematical model of oxygen diffusion and consumption to calculate oxygen profiles within the granuloma, assuming Michaelis–Menten kinetics. An approximate analytical solution—using a priori and newly estimated parameters from experimental data in a rabbit model of tuberculosis—was able to predict the size of hypoxic and necrotic regions in agreement with experimental results from the animal model. Such quantitative understanding of transport limitations can inform future tuberculosis therapeutic strategies that may include adjunct host-directed therapies that facilitate oxygen and drug delivery for more effective treatment.

DOI

10.1007/s10439-015-1415-3

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