Identification, modeling, and analysis of the dynamics of lactate and oxygen uptake during exercise in man

 
 
 
 

Identification, modeling, and analysis of the dynamics of lactate and oxygen uptake during exercise in man

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Title: Identification, modeling, and analysis of the dynamics of lactate and oxygen uptake during exercise in man
Author: Cabrera, Marco Eugenio
Description: In this study, the human bioenergetic system is identified and then modeled to relate cellular metabolism to whole-body responses during hypoxia and exercise. First, the dynamic characteristics of the physiological system are investigated using system identification methods. A time series model of the lactate concentration (LA) and oxygen uptake (VO2) response to incremental changes in work rate was fitted to simulated and experimental data. Time-varying system response parameters were determined and then examined. Two major transitions in the parameters were found to occur, at intensity levels equivalent to 53 ± 8% VO2max and 77 ± 9% VO2max. These changes in the parameters indicate that the best linear dynamic model that fits the observed system behavior has changed. The identified parameter changes over time suggest that the exercise intensity range (from rest to VO2max) is divided into three main intensity domains, each with distinct dynamics. Secondly, we developed a mathematical model of human bioenergetics that links cellular metabolism to whole-body responses. Our aim is to examine and quantify the mechanisms that control LA accumulation when O2 avail ability to the muscle is lowered. The model equations, which are based on dynamic mass balances for glycogen, glucose, pyruvate, LA, O2, and CO2, were solved numerically to simulate the system responses to hypoxia. The simulations predict (a) the substrate concentration changes in muscle, splanchnic bed, and other tissues, and (b) changes in other metabolites whose reactions are coupled to the main reactions processes. System responses to simulated respiratory and circulatory hypoxia were examined and compared to experimental data. Model simulations closely predicted the pattern of change in substrates and control metabolites to that from experimental data. A large decrease can occur in muscle O2 concentration without affecting muscle respiration. Only one-third of the increase in LA production can be attributed to changes in redox state (NADH/NAD).Thirdly, we extended the mathematical model to incorporate changes in metabolic rate. Our aim was to examine and quantify the mechanisms that control LA accumulation when the muscle O2 concentration is lowered with moderate exercise. Model simulations of system responses to exercise predict (a) the substrate concentration changes in muscle, splanchnic bed, and other tissues, and (b) changes in other metabolites whose reactions are coupled to the main reactions processes. System responses to a step change in metabolic rate were simulated, examined, and compared to experimental data. Model simulations closely predicted the pattern of change in substrates and control metabolites to that from experimental data. A large decrease can occur in muscle O2 concentration without affecting muscle respiration. Redox state decreased to 50% its initial value during exercise. With exercise initiation, LA increased abruptly, most likely as a result of a concurrent increase in pyruvate due to the sudden stimulation of glycolysis induced by the sharp rise in phosphorylation state. Therefore, during moderate exercise, (a) there are appropriate levels of oxyge nation at the tissue level even during the transient state, and (b) the observed increase in LA concentrations in the muscle and arterial blood are mainly due to the sudden increase in the glycolytic rate. (Abstract shortened by UMI)
Permanent Link: http://rave.ohiolink.edu/etdc/view?acc_num=case1058467730
http://hdl.handle.net/2374.OX/16580
Date: 1995

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