The Computational Integrated Myocyte: A View into the Virtual Heart

Bassingthwaighte, James B.; Vinnakota, Kalyan C.

doi:10.1196/annals.1302.034

Cited by 13 publications

(15 citation statements)

References 81 publications

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“…ATP to drive contraction, ion handling and other processes, is generated to match demand over this range of work, primarily by mitochondrial oxidative ATP synthesis 21,10 (Bass and Vinnak2004; Bass 2008). This variation persists in spite of the fact that all the cardiomyocytes are activated each beat as excitation spreads over the whole heart.…”

Section: Section IV Modeling and Analysis Of Cardiac Metabolismmentioning

confidence: 99%

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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Section: Section IV Modeling and Analysis Of Cardiac Metabolismmentioning

confidence: 99%

Modeling to Link Regional Myocardial Work, Metabolism and Blood Flows

et al. 2012

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“…With the progress in genomics and proteomics, it is becoming increasingly clear that this information does not reside in the genome alone, and probably not even in individual proteins that genes code for, as no real biological functionality is expressed at these levels (Noble, 2006a,b). There is growing recognition that to comprehend the true functioning of biological entities, it is necessary to understand complex molecular interactions in their natural cellular environment and precise spatio-temporal topology (Bassingthwaighte and Vinnakota, 2004;Greenstein et al, 2004) by defining essential concepts of regulatory systems forming their physiological behaviour.…”

Section: Introductionmentioning

confidence: 99%

Cardiac cell: a biological laser?

Chorvát

Chorvatova

2008

Biosystems

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“…Currently, computational models integrating cellular events into tissue and organ behavior utilize simplifications of the basic biophysical and biochemical models in order to reduce the complexity to practical computable levels. The "eternal cell" model [8], [9], focused as it is on cellular ion and substrate and energy regulation, is relatively simple but still complex enough that it has reduced forms for specific applications. Reductions compromise the adaptability of the models to respond correctly to dynamic changes in external inputs, for these normally require adjustments in rates at the biophysical, biochemical, and gene regulatory levels.…”

Section: Multiscale Modeling Of Cardiac Performance: Modeling Celmentioning

confidence: 99%

Strategies and Tactics in Multiscale Modeling of Cell-to-Organ Systems

2006

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Modeling is essential to integrating knowledge of human physiology. Comprehensive self-consistent descriptions expressed in quantitative mathematical form define working hypotheses in testable and reproducible form, and though such models are always "wrong" in the sense of being incomplete or partly incorrect, they provide a means of understanding a system and improving that understanding. Physiological systems, and models of them, encompass different levels of complexity. The lowest levels concern gene signaling and the regulation of transcription and translation, then biophysical and biochemical events at the protein level, and extend through the levels of cells, tissues and organs all the way to descriptions of integrated systems behavior. The highest levels of organization represent the dynamically varying interactions of billions of cells. Models of such systems are necessarily simplified to minimize computation and to emphasize the key factors defining system behavior; different model forms are thus often used to represent a system in different ways. Each simplification of lower level complicated function reduces the range of accurate operability at the higher level model, reducing robustness, the ability to respond correctly to dynamic changes in conditions. When conditions change so that the complexity reduction has resulted in the solution departing from the range of validity, detecting the deviation is critical, and requires special methods to enforce adapting the model formulation to alternative reduced-form modules or decomposing the reduced-form aggregates to the more detailed lower level modules to maintain appropriate behavior. The processes of error recognition, and of mapping between different levels of model complexity and shifting the levels of complexity of models in response to changing conditions, are essential for adaptive modeling and computer simulation of large-scale systems in reasonable time.

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The Computational Integrated Myocyte: A View into the Virtual Heart

Cited by 13 publications

References 81 publications

Modeling to Link Regional Myocardial Work, Metabolism and Blood Flows

Modeling to Link Regional Myocardial Work, Metabolism and Blood Flows

Cardiac cell: a biological laser?

Strategies and Tactics in Multiscale Modeling of Cell-to-Organ Systems

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