Circulation: Overall Regulation

Guyton, Arthur C.; Coleman, Thomas G.; Granger, Harris J.

doi:10.1146/annurev.ph.34.030172.000305

Cited by 776 publications

(507 citation statements)

References 61 publications

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“…There is a long tradition in physiology and biochemistry of building ordinary differential equation (ODE) models of a broad diversity of systems (Guyton et al 1972;Ten Tusscher et al 2004;Keener and Sneyd 2009). One of the challenges in building a model that accurately simulates the properties of a biological system is that we often do not know the entire network that might be relevant, nor all the kinetics that link all the variables.…”

Section: Mathematical Models Of Biological Systemsmentioning

confidence: 99%

Systems Biology of Phenotypic Robustness and Plasticity

Nijhout

Sadre-Marandi

Best

et al. 2017

Integrative and Comparative Biology

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Synopsis Gene regulatory networks, cellular biochemistry, tissue function, and whole body physiology are imbued with myriad overlapping and interacting homeostatic mechanisms that ensure that many phenotypes are robust to genetic and environmental variation. Animals also often have plastic responses to environmental variables, which means that many different phenotypes can correspond to a single genotype. Since natural selection acts on phenotypes, this raises the question of how selection can act on the genome if genotypes are decoupled from phenotypes by robustness and plasticity mechanisms. The answer can be found in the systems biology of the homeostatic mechanisms themselves. First, all such mechanisms operate over a limited range and outside that range the controlled variable changes rapidly allowing natural selection to act. Second, mutations and environmental stressors can disrupt homeostatic mechanisms, exposing cryptic genetic variation and allowing natural selection to act. We illustrate these ideas by examining the systems biology of four specific examples. We show how it is possible to analyze and visualize the roles of specific genes and specific polymorphisms in robustness in the context of large and realistic nonlinear systems. We also describe a new method, system population models, that allows one to connect causal dynamics to the variable outcomes that one sees in biological populations with large variation.

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Section: Mathematical Models Of Biological Systemsmentioning

confidence: 99%

Systems Biology of Phenotypic Robustness and Plasticity

Nijhout

Sadre-Marandi

Best

et al. 2017

Integrative and Comparative Biology

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“…Over thirty years ago, Dr. Arthur Guyton suggested that circulatory physiology was starting to change into and use the techniques of engineering science [1] and his model made large strides towards this change. Unfortunately, his famous circulatory physiology model has not developed significantly since 1992 in the practical form of a block diagram of systems and subsystems.…”

Section: Discussionmentioning

confidence: 99%

“…Since the model size, and number of variables and parameters, has increased immensely since the first version of the model from 1972, multiple layers of subsystems were used. At the lowest level, a first order dynamic system was implemented as in the original model diagram [1] with an integrator, a gain and a summer, as in Fig. 4, and was subsequently 'masked' as a transfer function in the s-domain in the form of:…”

Section: Guyton's Model In Simulinkmentioning

confidence: 99%

“…A sample 'reference' experiment, similar to those described in [1,52], was simulated by reducing kidney mass to 30% of normal and increasing salt intake to 9 times normal at the start of the experiment. The responses of the MODSIM implementation and our Simulink version of the model are shown in Fig.…”

Section: Guyton's Model In Simulinkmentioning

confidence: 99%

“…At the time of its conception (1972), the integrated physiology model developed by Guyton [1] was a breakthrough in many respects:…”

Section: Introductionmentioning

confidence: 99%

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Graphical simulation environments for modelling and simulation of integrative physiology

Mangourova

Ringwood

Vliet

2011

Computer Methods and Programs in Biomedicine

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c o m p u t e r m e t h o d s a n d p r o g r a m s i n b i o m e d i c i n e 1 0 2 ( 2 0 1 1 ) [295][296][297][298][299][300][301][302][303][304] j o u r n a l h o m e p a g e : w w w . i n t l . e l s e v i e r h e a l t h . IntroductionAt the time of its conception (1972), the integrated physiology model developed by Guyton [1] was a breakthrough in many respects:(1) It assembled the available knowledge on the dynamics of the body's circulatory components and how they interacted with each other, (2) It presented a diagrammatic form, which allowed the totality of the model to be viewed and interactions examined, and (3) The model was specified using the basic components of integrators, summers and (sometimes nonlinear) gains, the fundamental building blocks of analogue computers, facilitating computation. * Corresponding author. Tel.: +353 879886557.E-mail address: violeta.i.mangourova@nuim.ie (V. Mangourova).Clearly, the longevity of this model is testament to its quality and usefulness. Unfortunately, developments in integrative physiological modelling have not kept pace with further discoveries in physiological science and developments in computing. In particular, the absence of an agreed computing platform, which can serve current teaching and research purposes, and be added to and updated by the physiology community at large, is disappointing. Recently, a number of large-scale initiatives have emerged, such as the IUPS (International Union of Physiological Sciences) Physiome Project [2], which attempt to directly address this issue. However, there is the issue of the universal adoption of a single standard in a situation where a number of competing standards exist and the associated question as to whether a single computing platform can cater for needs at all levels of detail and timescale. Furthermore, in the multi-disciplinary world of physiological modelling, where mathematicians, engineers, scientists 0169-2607/$ -see front matter

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Hypertension

Guyton

1988

Arch Neurol

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Circulation: Overall Regulation

Cited by 776 publications

References 61 publications

Systems Biology of Phenotypic Robustness and Plasticity

Systems Biology of Phenotypic Robustness and Plasticity

Graphical simulation environments for modelling and simulation of integrative physiology

Hypertension

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