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A computational model of oxygen delivery by hemoglobin-based oxygen carriers in three-dimensional microvascular networks.

ABSTRACT: A detailed computational model is developed to simulate oxygen transport from a three-dimensional (3D) microvascular network to the surrounding tissue in the presence of hemoglobin-based oxygen carriers. The model accounts for nonlinear O(2) consumption, myoglobin-facilitated diffusion and nonlinear oxyhemoglobin dissociation in the RBCs and plasma. It also includes a detailed description of intravascular resistance to O(2) transport and is capable of incorporating realistic 3D microvascular network geometries. Simulations in this study were performed using a computer-generated microvascular architecture that mimics morphometric parameters for the hamster cheek pouch retractor muscle. Theoretical results are presented next to corresponding experimental data. Phosphorescence quenching microscopy provided PO(2) measurements at the arteriolar and venular ends of capillaries in the hamster retractor muscle before and after isovolemic hemodilution with three different hemodilutents: a non-oxygen-carrying plasma expander and two hemoglobin solutions with different oxygen affinities. Sample results in a microvascular network show an enhancement of diffusive shunting between arterioles, venules and capillaries and a decrease in hemoglobin's effectiveness for tissue oxygenation when its affinity for O(2) is decreased. Model simulations suggest that microvascular network anatomy can affect the optimal hemoglobin affinity for reducing tissue hypoxia. O(2) transport simulations in realistic representations of microvascular networks should provide a theoretical framework for choosing optimal parameter values in the development of hemoglobin-based blood substitutes.

SUBMITTER: Tsoukias NM

PROVIDER: S-EPMC2741314 | biostudies-literature | 2007 Oct

REPOSITORIES: biostudies-literature

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A computational model of oxygen delivery by hemoglobin-based oxygen carriers in three-dimensional microvascular networks.

Tsoukias Nikolaos M NM Goldman Daniel D Vadapalli Arjun A Pittman Roland N RN Popel Aleksander S AS

Journal of theoretical biology 20070616 4

A detailed computational model is developed to simulate oxygen transport from a three-dimensional (3D) microvascular network to the surrounding tissue in the presence of hemoglobin-based oxygen carriers. The model accounts for nonlinear O(2) consumption, myoglobin-facilitated diffusion and nonlinear oxyhemoglobin dissociation in the RBCs and plasma. It also includes a detailed description of intravascular resistance to O(2) transport and is capable of incorporating realistic 3D microvascular net ...[more]

PMID: 17686494

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Project description:Transforming Growth Factor (TGF-beta1) is a member of the TGF-beta superfamily ligand-receptor network. and plays a crucial role in tissue regeneration. The extensive in vitro and in vivo experimental literature describing its actions nevertheless describe an apparent paradox in that during re-epithelialisation it acts as proliferation inhibitor for keratinocytes. The majority of biological models focus on certain aspects of TGF-beta1 behaviour and no one model provides a comprehensive story of this regulatory factor's action. Accordingly our aim was to develop a computational model to act as a complementary approach to improve our understanding of TGF-beta1. In our previous study, an agent-based model of keratinocyte colony formation in 2D culture was developed. In this study this model was extensively developed into a three dimensional multiscale model of the human epidermis which is comprised of three interacting and integrated layers: (1) an agent-based model which captures the biological rules governing the cells in the human epidermis at the cellular level and includes the rules for injury induced emergent behaviours, (2) a COmplex PAthway SImulator (COPASI) model which simulates the expression and signalling of TGF-beta1 at the sub-cellular level and (3) a mechanical layer embodied by a numerical physical solver responsible for resolving the forces exerted between cells at the multi-cellular level. The integrated model was initially validated by using it to grow a piece of virtual epidermis in 3D and comparing the in virtuo simulations of keratinocyte behaviour and of TGF-beta1 signalling with the extensive research literature describing this key regulatory protein. This research reinforces the idea that computational modelling can be an effective additional tool to aid our understanding of complex systems. In the accompanying paper the model is used to explore hypotheses of the functions of TGF-beta1 at the cellular and subcellular level on different keratinocyte populations during epidermal wound healing.

Dataset Information

A computational model of oxygen delivery by hemoglobin-based oxygen carriers in three-dimensional microvascular networks.

Publications

A computational model of oxygen delivery by hemoglobin-based oxygen carriers in three-dimensional microvascular networks.

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