Computational modeling of cardiac fatty acid uptake and utilization

Musters, Mark; Bassingthwaighte, Jim B.; Panday, Virjanand; Riel, Natal A. W. van; Vusse, Ger J.

doi:10.1016/s1569-2558(03)33010-3

Cited by 3 publications

(6 citation statements)

References 72 publications

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“…A constant supply of both uFAs and FA-albumin complexes is the source of this model at x = 0. [21,24] and are listed in Table 1. At x = x ECM , 'no flux' boundary conditions were defined [21]; the myocardial cytoplasm was considered to be a sink for uFAs; the sarcolemma was impermeable for albumin and its complexes:…”

Section: Boundary and Initial Conditionsmentioning

confidence: 99%

“…The partial derivatives in Eqns 1-5 were replaced with central, second-order, finite differences, as was done previously [21,24]. A spatial discretisation of 50 segments was applied, which gave an accurate approximation of the partial derivatives in Eqns 1-5 when tested against using more segments [24]. The resulting set of first-order equations were solved with ode15s, a 'stiff' differential equation solver in MATLAB 6.5 (The MathWorks, Inc.).…”

Section: Parameter Values Simulation Procedures and Experimental Valmentioning

confidence: 99%

“…We recently calculated that the maximal rate of FA transfer across the sarcolemma achievable by unmediated diffusion of uFAs at their ambient interstitial concentrations does not exceed 15 nmol/(g min) [24]. This rate is obviously too low to explain the normal FA influx of 65 to 85 nmol/(g min) observed in the intact heart.…”

Section: Introductionmentioning

confidence: 99%

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Computational evidence for protein-mediated fatty acid transport across the sarcolemma

Musters

Bassingthwaighte

Riel

et al. 2006

Biochemical Journal

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Long-chain fatty acids (FAs) are important substrates used by the heart to fulfil its energy requirements. Prior to mitochondrial oxidation, blood-borne FAs must pass through the cell membrane of the cardiac myocyte (sarcolemma). The mechanism underlying the sarcolemmal transport of FAs is incompletely understood. The aim of the present study was to estimate the trans-sarcolemmal FA uptake rate using a comprehensive computer model, in which the most relevant mechanisms proposed for cardiac FA uptake were incorporated. Our in silico findings show that diffusion of FA, present in its unbound form (uFA) in close proximity to the outer leaflet of the sarcolemma and serving as sole FA source, is insufficient to account for the physiological FA uptake rate. The inclusion of a hypothetical membrane-associated FA-TFPC (FA-transport-facilitating protein complex) in the model calculations substantially increased the FA uptake rate across the sarcolemma. The model requires that the biological properties of the FA-TFPC allow for increasing the rate of absorption of FA into the outer leaflet and the 'flip-flop' rate of FA from the outer to the inner leaflet of the sarcolemma. Experimental studies have identified various sarcolemma-associated proteins promoting cardiac FA uptake. It remains to be established whether these proteins possess the properties predicted by our model. Our findings also indicate that albumin receptors located on the outer leaflet of the sarcolemma facilitate the transfer of FA across the membrane to a significant extent. The outcomes of the computer simulations were verified with physiologically relevant FA uptake rates as assessed in the intact, beating heart in experimental studies.

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Section: Boundary and Initial Conditionsmentioning

confidence: 99%

Section: Parameter Values Simulation Procedures and Experimental Valmentioning

confidence: 99%

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Computational evidence for protein-mediated fatty acid transport across the sarcolemma

Musters

Bassingthwaighte

Riel

et al. 2006

Biochemical Journal

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“…Many phenomena of interest in physiology and biochemistry are characterized by reactions among several chemical species and diffusion in various mediums (see [6][7][8]10]). In a closed system, both reactions and diffusion are governed by a system of ordinary differential equations (ODEs) y(t) = M y(t), (1.1) which guarantees conservation of the total amount of y(t) for any t ≥ 0.…”

Section: Introductionmentioning

confidence: 99%

Absolutely Stable Explicit Schemes for Reaction Systems

Lee¹,

Leem²,

Park³

et al. 2010

Journal of the Korean Mathematical Society

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Abstract. We introduce two numerical schemes for solving a system of ordinary differential equations which characterizes several kinds of linear reactions and diffusion from biochemistry, physiology, etc. The methods consist of sequential applications of the simple exact solver for a reversible reaction. We prove absolute stability and convergence of the proposed explicit methods. One is of first order and the other is of second order. Numerical results are included.

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“…Many phenomena of interest in physiology and biochemistry are characterized by reactions among several chemical species and diffusion in various mediums (see [4][5][6][7]). In a closed system, both reactions and diffusion are governed by a system of ordinary differential equations (ODEs)ẏ…”

Section: Introductionmentioning

confidence: 99%

Absolutely stable explicit schemes for reaction systems.

Lee

Leem

Park

et al. 2007

Proc Appl Math and Mech

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Many phenomena of interest in physiology and biochemistry are characterized by reactions among several chemical species and diffusion in various mediums (see [4][5][6][7]). In a closed system, both reactions and diffusion are governed by a system of ordinary differential equations (ODEs)ẏwhich guarantees conservation of the total amount of y(t) for any t ≥ 0. Since we are concerned with the steady-state solution as well as the transient in simulations of very large systems of chemical reactions or molecular dynamics, we need to take the overall computational cost into consideration. Many physiologists and biochemists prefer explicit methods to implicit methods since implementation of the explicit methods is easier than the others. The popular methods for reaction systems are simple explicit schemes such as Euler's method, Runge-Kutta method, etc. However, it is well-known that conditional stability, the typical weak point of explicit methods, is very fatal for stiff problems. In the past few decades, many studies on numerical methods for stiff ODEs have been done in various aspects (see [1][2][3]).The aim of this talk is to present two absolutely stable explicit schemes which are applicable to a general reaction system (1). The proposed methods are motivated by the simple exact solver for a reversible reaction. In spite of their explicitness, we have unconditional stability, that is, stability without any condition on the step size. Furthermore, we proved the convergence of the proposed methods; one is of first order and the other is of second order.

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Computational modeling of cardiac fatty acid uptake and utilization

Cited by 3 publications

References 72 publications

Computational evidence for protein-mediated fatty acid transport across the sarcolemma

Computational evidence for protein-mediated fatty acid transport across the sarcolemma

Absolutely Stable Explicit Schemes for Reaction Systems

Absolutely stable explicit schemes for reaction systems.

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