A computational model of oxygen transport from red blood cells to mitochondria

Beyer, Richard P.; Bassingthwaighte, James B.; Deußen, Andreas

doi:10.1016/s0169-2607(00)00146-2

Cited by 13 publications

(21 citation statements)

References 26 publications

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“…13 In contrast, TOMS731 is considerably faster than TOMS690, and the solutions are equally accurate. All the results presented in this paper were obtained using the This model's capabilities extend those of the previous models, 20,27,51,55 and it is computationally fast in spite of its comprehensive nature, so this model is our preferred vehicle for data analysis for oxygen-related studies, for example for 15 O-oxygen studies using positron emission tomography where many regions of interest are analyzed within an organ. The model is available for download and public use from the Physiome website at: http:/nsr.bioeng.washington.edu/jsim/models/webmodel/NSR/ Exchange_O2_CO2_HCO3_and_H/…”

Section: Methodsmentioning

confidence: 93%

“…Given the rapid dissipation of intracapillary radial concentration gradients, the RBC can be well represented as a central column of fluid surrounded by plasma, a situation mathematically similar to Hb being dispersed throughout the plasma. 20,51 (This assumption fails at low hematocrits, Hct, as shown by Hellums 36 ). The RBC and plasma move by plug flow with different velocities; RBC move faster than the plasma, being in the higher velocity central stream.…”

Section: Blood-tissue Exchange Unit and Nomenclaturementioning

confidence: 99%

“…Oxygen (O 2 ) transport and metabolism involves convection, diffusion, permeation, chemical reactions, binding and facilitated transport. 20,51,54 Oxygen's binding to hemoglobin (Hb) is affected directly by carbon dioxide (CO 2 ) levels, pH, temperature, and 2,3-diphosphoglycerate (2,3-DPG) levels, and affected indirectly therefore by bicarbonate ( ) buffering, metabolism and tissue acidification, renal acid and base handling, and the hemoglobin mediated nonlinear O 2 -CO 2 interactions. 26,37,44,63 A decrease in pH or an increase in CO 2 partial pressure (P CO 2 ) in the systemic capillaries reduces the affinity of Hb for O 2 (the Bohr effect) and enhances the delivery of O 2 to tissue.…”

Section: Introductionmentioning

confidence: 99%

“…The interpretation and understanding of alveoli-blood or blood-tissue gas exchange, whether being assessed from the observations of arterial and venous O 2 concentrations, 20,51,54 or by intra-tissue chemical signals such as BOLD MRI 46,53 or hemoglobin and myoglobin spectra, 59,60 or by external detection of tracer content such as 15 O-oxygen and 15 O-water through PET studies, 27,51,55,62 depends in general on all the factors involved in the dissociation of oxyhemoglobin. To study the dynamics of O 2 transport and metabolism, it is therefore important to account for the transport and exchange of CO 2 , , and H + as well as O 2 -CO 2 interactions.…”

Section: Introductionmentioning

confidence: 99%

“…Reviews by Hellums et al 37 and Popel 54 and recent studies oriented toward PET 15 O-oxygen image analysis by Beyer et al, 20 Deussen and Bassingthwaighte, 27 and Li et al 51 illustrate the applicability of the geometry that Krogh modeled. Other models based on non-cylindrical geometry have been designed or proposed to reflect the morphological and anatomical structures of the specific tissues.…”

Section: Introductionmentioning

confidence: 99%

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Simultaneous Blood–Tissue Exchange of Oxygen, Carbon Dioxide, Bicarbonate, and Hydrogen Ion

Dash

Bassingthwaighte

2006

Ann Biomed Eng

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A detailed nonlinear four-region (red blood cell, plasma, interstitial fluid, and parenchymal cell) axially distributed convection-diffusion-permeation-reaction-binding computational model is developed to study the simultaneous transport and exchange of oxygen (O 2 ) and carbon dioxide (CO 2 ) in the blood-tissue exchange system of the heart. Since the pH variation in blood and tissue influences the transport and exchange of O 2 and CO 2 (Bohr and Haldane effects), and since most CO 2 is transported as (bicarbonate) via the CO 2 hydration (buffering) reaction, the transport and exchange of and H + are also simulated along with that of O 2 and CO 2 . Furthermore, the model accounts for the competitive nonlinear binding of O 2 and CO 2 with the hemoglobin inside the red blood cells (nonlinear O 2 -CO 2 interactions, Bohr and Haldane effects), and myoglobin-facilitated transport of O 2 inside the parenchymal cells. The consumption of O 2 through cytochrome-c oxidase reaction inside the parenchymal cells is based on MichaelisMenten kinetics. The corresponding production of CO 2 is determined by respiratory quotient (RQ), depending on the relative consumption of carbohydrate, protein, and fat. The model gives a physiologically realistic description of O 2 transport and metabolism in the microcirculation of the heart. Furthermore, because model solutions for tracer transients and steady states can be computed highly efficiently, this model may be the preferred vehicle for routine data analysis where repetitive solutions and parameter optimization are required, as is the case in PET imaging for estimating myocardial O 2 consumption.

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Section: Methodsmentioning

confidence: 93%

Section: Blood-tissue Exchange Unit and Nomenclaturementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Simultaneous Blood–Tissue Exchange of Oxygen, Carbon Dioxide, Bicarbonate, and Hydrogen Ion

Dash

Bassingthwaighte

2006

Ann Biomed Eng

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The Pathway for Oxygen: Tutorial Modelling on Oxygen Transport from Air to Mitochondrion

Bassingthwaighte

Raymond

Dash

et al. 2016

Advances in Experimental Medicine and Biology

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The ‘Pathway for Oxygen’ is captured in a set of models describing quantitative relationships between fluxes and driving forces for the flux of oxygen from the external air source to the mitochondrial sink at cytochrome oxidase. The intervening processes involve convection, membrane permeation, diffusion of free and heme-bound O2 and enzymatic reactions. While this system’s basic elements are simple: ventilation, alveolar gas exchange with blood, circulation of the blood, perfusion of an organ, uptake by tissue, and consumption by chemical reaction, integration of these pieces quickly becomes complex. This complexity led us to construct a tutorial on the ideas and principles; these first PathwayO2 models are simple but quantitative and cover: 1) a ‘one-alveolus lung’ with airway resistance, lung volume compliance, 2) bidirectional transport of solute gasses like O2 and CO2, 3) gas exchange between alveolar air and lung capillary blood, 4) gas solubility in blood, and circulation of blood through the capillary syncytium and back to the lung, and 5) blood-tissue gas exchange in capillaries. These open-source models are at Physiome.org and provide background for the many respiratory models there.

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Modeling to Link Regional Myocardial Work, Metabolism and Blood Flows

et al. 2012

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Given the mono-functional, highly coordinated processes of cardiac excitation and contraction, the observations that regional myocardial blood flows, rMBF, are broadly heterogeneous has provoked much attention, but a clear explanation has not emerged. In isolated and in vivo heart studies the total coronary flow is found to be proportional to the rate-pressure product (systolic mean blood pressure times heart rate), a measure of external cardiac work. The same relationship might be expected on a local basis: more work requires more flow. The validity of this expectation has never been demonstrated experimentally. In this article we review the concepts linking cellular excitation and contractile work to cellular energetics and ATP demand, substrate utilization, oxygen demand, vasoregulation, and local blood flow. Mathematical models of these processes are now rather well developed. We propose that the construction of an integrated model encompassing the biophysics, biochemistry and physiology of cardiomyocyte contraction, then combined with a detailed three-dimensional structuring of the fiber bundle and sheet arrangements of the heart as a whole will frame an hypothesis that can be quantitatively evaluated to settle the prime issue: Does local work drive local flow in a predictable fashion that explains the heterogeneity? While in one sense one can feel content that work drives flow is irrefutable, there are no cardiac contractile models that demonstrate the required heterogeneity in local strain-stress-work; quite the contrary, cardiac contraction models have tended toward trying to show that work should be uniform. The object of this review is to argue that uniformity of work does not occur, and is impossible in any case, and that further experimentation and analysis are necessary to test the hypothesis.

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A computational model of oxygen transport from red blood cells to mitochondria

Cited by 13 publications

References 26 publications

Simultaneous Blood–Tissue Exchange of Oxygen, Carbon Dioxide, Bicarbonate, and Hydrogen Ion

Simultaneous Blood–Tissue Exchange of Oxygen, Carbon Dioxide, Bicarbonate, and Hydrogen Ion

The Pathway for Oxygen: Tutorial Modelling on Oxygen Transport from Air to Mitochondrion

Modeling to Link Regional Myocardial Work, Metabolism and Blood Flows

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