NDLI: Modeling Cellular Metabolism and Energetics in Skeletal Muscle: Large-Scale Parameter Estimation and Sensitivity Analysis

Content Provider	IEEE Xplore Digital Library
Author	Dash, R.K. Yanjun Li Jaeyeon Kim Saidel, G.M. Cabrera, M.E.
Copyright Year	1964
Abstract	Skeletal muscle plays a major role in the regulation of whole-body energy metabolism during physiological stresses such as ischemia, hypoxia, and exercise. Current experimental techniques provide relatively little in vivo data on dynamic responses of metabolite concentrations and metabolic fluxes in skeletal muscle to such physiological stimuli. As a complementary approach to experimental measurements and as a framework for quantitatively analyzing available in vivo data, a physiologically based model of skeletal muscle cellular metabolism and energetics is developed. This model, which incorporates key transport and reaction processes, is based on dynamic mass balances of 30 chemical species in capillary (blood) and tissue (cell) domains. The reaction fluxes in the cellular domain are expressed in terms of a generalized Michaelis-Menten equation involving energy controller ratios ATP/ADP and NADH/NAD⁺. This formalism introduces a large number of unknown parameters (~90). Estimating these parameters from in vivo sparse data and evaluating dynamic sensitivities of the model outputs with respect to these parameters is a challenging problem. Parameter estimation is accomplished using an efficient, nonlinear, constraint-based, optimization algorithm that minimizes differences between available experimental data and corresponding model outputs by explicitly utilizing equality constraints on resting fluxes and concentrations. With the estimated parameter values, the model is able to simulate dynamic responses to reduced blood flow (ischemia) of key metabolite concentrations and metabolic fluxes, both measured and nonmeasured. A general parameter sensitivity analysis is carried out to determine and characterize the parameters having the most and least effects on the measured outputs.
Sponsorship	IEEE Engineering in Medicine and Biology Society
Page Count	21
File Size	2596167
Starting Page	1298
Ending Page	1318
File Format	PDF
ISSN	00189294
Volume Number	55
Issue Number	4
Language	English
Publisher	Institute of Electrical and Electronics Engineers, Inc. (IEEE)
Publisher Date	2008-04-01
Publisher Place	U.S.A.
Access Restriction	One Nation One Subscription (ONOS)
Rights Holder	Institute of Electrical and Electronics Engineers, Inc. (IEEE)
Subject Keyword	Biochemistry Muscles Large-scale systems Parameter estimation Sensitivity analysis In vivo Ischemic pain Stress Energy measurement Chemical processes Mathematical modeling; computer simulation; dynamic mass balances; skeletal muscle; cellular metabolism; ischemia; optimal parameter estimation; sensitivity analysis Optimal parameter estimation Computer simulation Dynamic mass balances Ischemia Mathematical modeling
Content Type	Text
Resource Type	Article
Subject	Biomedical Engineering

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3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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