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WIREs Syst Biol Med
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Integrative approaches for modeling regulation and function of the respiratory system

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Mathematical models have been central to understanding the interaction between neural control and breathing. Models of the entire respiratory system—which comprises the lungs and the neural circuitry that controls their ventilation—have been derived using simplifying assumptions to compartmentalize each component of the system and to define the interactions between components. These full system models often rely—through necessity—on empirically derived relationships or parameters, in addition to physiological values. In parallel with the development of whole respiratory system models are mathematical models that focus on furthering a detailed understanding of the neural control network, or of the several functions that contribute to gas exchange within the lung. These models are biophysically based, and rely on physiological parameters. They include single‐unit models for a breathing lung or neural circuit, through to spatially distributed models of ventilation and perfusion, or multicircuit models for neural control. The challenge is to bring together these more recent advances in models of neural control with models of lung function, into a full simulation for the respiratory system that builds upon the more detailed models but remains computationally tractable. This requires first understanding the mathematical models that have been developed for the respiratory system at different levels, and which could be used to study how physiological levels of O2 and CO2 in the blood are maintained. WIREs Syst Biol Med 2013, 5:687–699. doi: 10.1002/wsbm.1244 This article is categorized under: Models of Systems Properties and Processes > Mechanistic Models Physiology > Mammalian Physiology in Health and Disease Models of Systems Properties and Processes > Organ, Tissue, and Physiological Models

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Mean response of minute ventilation to 7, 6, 5, and 3% inspired CO2 in 10 human subjects except for 7% where the mean response is in 14 human subjects. The data were extracted from Figure 10 of Ref using the ENGAUGE software available from http://sourceforge.net. (Reprinted with permission from Ref . Copyright 1970 American Physiological Society)
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General features of a feedback regulator. (Reprinted with permission from Ref . Copyright 1954 American Physiological Society)
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A schematic description of the respiratory system and other organs with which it interacts.
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Mean response of minute ventilation in 10 human subjects to 9% inspired O2. The upper curve shows the results when the alveolar CO2 concentration was controlled. The data were extracted from Figure 8 of Ref using the ENGAUGE software available from http://sourceforge.net. (Reprinted with permission from Ref Copyright 1973 American Physiological Society)
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Models of Systems Properties and Processes > Mechanistic Models
Physiology > Mammalian Physiology in Health and Disease
Models of Systems Properties and Processes > Organ, Tissue, and Physiological Models

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