Linking Pulmonary Oxygen Uptake, Muscle Oxygen Utilization and Cellular Metabolism during Exercise

Lai, Nicola; Camesasca, Marco; Saidel, Gerald M.; Dash, Ranjan K.; Cabrera, Marco E.

doi:10.1007/s10439-007-9271-4

Cited by 23 publications

(44 citation statements)

References 67 publications

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“…Although model validation was not possible, PC and Pi model simulations were in agreement with 31 P-MRS data obtained on forearm flexor muscle. This model provided a quantitative approach to study cellular energy metabolism in intact stimulated muscle and was successfully integrated to multi-level system models to investigate O 2 transport in whole-skeletal muscle at various increased levels of energy demand [69,71,75] and environmental conditions [74].…”

Section: Whole-muscle Model Of Muscle Contraction and Energeticsmentioning

confidence: 99%

“…Several computational models at various scales and degrees of complexity have been developed and validated to investigate the regulation of skeletal muscle energetics during exercise [68,69,70,71,72]. The strategy for building these whole-body, multi-scale models has been to choose the level of detail and complexity of the processes of transport and metabolism that are required to test mechanisms of metabolic regulation and to make predictions of the responses to exercise in humans.…”

Section: Multi-level System Models Of Exercisementioning

confidence: 99%

“…The model takes into account the dynamics of O 2 stores in blood and tissue and muscle O 2 consumption is estimated from measurements of StO 2m and VO 2p . This model was then enhanced to investigate factors affecting muscle O 2 utilization during exercise by linking ATP formation from oxidative phosphorylation and net PC breakdown to the rate of ATP hydrolysis [71]. Then, the dynamics of the metabolic flux rates of oxidative phosphorylation, ATP hydrolysis, and the forward and reverse rates of the creatine kinase reaction were simulated in the large muscle groups used in cycling.…”

Section: Multi-level System Models Of Exercisementioning

confidence: 99%

“…Model validation with experimental data in vivo Limited experimental data for estimation of model parameters [68][69][70][71][72][73][74][75][76][77] Drug Discov Today Dis Models. Author manuscript; available in PMC 2014 January 11.…”

Section: Amentioning

confidence: 99%

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Models of muscle contraction and energetics

Lai

Gladden

Carlier

et al. 2008

Drug Discovery Today: Disease Models

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How does skeletal muscle manage to regulate the pathways of ATP synthesis during large-scale changes in work rate while maintaining metabolic homeostasis remains unknown. The classic model of metabolic regulation during muscle contraction states that accelerating ATP utilization leads to increasing concentrations of ADP and Pi, which serve as substrates for oxidative phosphorylation and thus accelerate ATP synthesis. An alternative model states that both the ATP demand and ATP supply pathways are simultaneously activated. Here, we review experimental and computational models of muscle contraction and energetics at various organizational levels and compare them with respect to their pros and cons in facilitating understanding of the regulation of energy metabolism during exercise in the intact organism.Keywords computer models; energy metabolism; regulation; exercise; in vivo models; single fiber Skeletal muscle has the extraordinary capacity to adjust to an immediate increase in energy demand. The dynamic response of the energetic system of a muscle cell to increased work or exercise is one of the most important aspects of cell functioning. At rest, both the concentration of adenosine triphosphate (ATP) in skeletal muscle and the ATP turnover rate are relatively low [1]. During muscle contraction, however, the rate of ATP utilization can increase by up to two orders of magnitude, while muscle ATP concentration remains near resting levels [2]. Maintenance of ATP homeostasis in working muscle during large-scale changes in ATP turnover rates requires close coupling of ATPase flux with ATP synthase flux [3]. Moreover, it requires precise coordination of the ATP-supply pathways (phosphagenic, glycolytic, and oxidative), each with distinct flux and energy capacities [4], to match the dynamics of ATP utilization. Surprisingly, while the flux through these energetic pathways increases in proportion to the energy demand, the concentrations of

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Section: Whole-muscle Model Of Muscle Contraction and Energeticsmentioning

confidence: 99%

Section: Multi-level System Models Of Exercisementioning

confidence: 99%

Section: Multi-level System Models Of Exercisementioning

confidence: 99%

Section: Amentioning

confidence: 99%

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Models of muscle contraction and energetics

Lai

Gladden

Carlier

et al. 2008

Drug Discovery Today: Disease Models

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“…To evaluate the effects of extra-vascular volume and blood volume distribution during exercise, a mathematical model was applied to quantify how these factors affect oxygen transport and utilization. 5,6,7 The mathematical model presented here is used to examine the effect of local muscle blood-tissue volume distribution on the responses of muscle oxygen saturation during exercise. Together with NIRS data, optimal estimates can be obtained of maximal metabolic flux ( V max ) and blood flow increase (Δ Q ) during exercise.…”

Section: Introductionmentioning

confidence: 99%

Non-Invasive Estimation Of Metabolic Flux And Blood Flow In Working Muscle: Effect Of Blood-Tissue Distribution

Lai

Saidel

Iorio

et al. 2009

Advances in Experimental Medicine and Biology

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Muscle oxygenation measurements by near infrared spectroscopy (NIRS) are frequently obtained in humans to make inferences about mechanisms of metabolic control of respiration in working skeletal muscle. However, these measurements have technical limitations that can mislead the evaluation of tissue processes. In particular, NIRS measurements of working muscle represent oxygenation of a mix of fibers with heterogeneous activation, perfusion and architecture. Specifically, the relative volume distribution of capillaries, small arteries, and venules may affect NIRS data. To determine the effect of spatial volume distribution of components of working muscle on oxygen utilization dynamics and blood flow changes, a mathematical model of oxygen transport and utilization was developed. The model includes blood volume distribution within skeletal muscle and accounts for convective, diffusive, and reactive processes of oxygen transport and metabolism in working muscle. Inputs to the model are arterial O2 concentration, cardiac output and ATP demand. Model simulations were compared to exercise data from human subjects during a rest-to-work transition. Relationships between muscle oxygen consumption, blood flow, and the rate coefficient of capillary-tissue transport are analyzed. Blood volume distribution in muscle has noticeable effects on the optimal estimates of metabolic flux and blood flow in response to an exercise stimulus.

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Exercise: Kinetic Considerations for Gas Exchange

Rossiter

2010

Comprehensive Physiology

162

255

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The activities of daily living typically occur at metabolic rates below the maximum rate of aerobic energy production. Such activity is characteristic of the nonsteady state, where energy demands, and consequential physiological responses, are in constant flux. The dynamics of the integrated physiological processes during these activities determine the degree to which exercise can be supported through rates of O₂ utilization and CO₂ clearance appropriate for their demands and, as such, provide a physiological framework for the notion of exercise intensity. The rate at which O₂ exchange responds to meet the changing energy demands of exercise--its kinetics--is dependent on the ability of the pulmonary, circulatory, and muscle bioenergetic systems to respond appropriately. Slow response kinetics in pulmonary O₂ uptake predispose toward a greater necessity for substrate-level energy supply, processes that are limited in their capacity, challenge system homeostasis and hence contribute to exercise intolerance. This review provides a physiological systems perspective of pulmonary gas exchange kinetics: from an integrative view on the control of muscle oxygen consumption kinetics to the dissociation of cellular respiration from its pulmonary expression by the circulatory dynamics and the gas capacitance of the lungs, blood, and tissues. The intensity dependence of gas exchange kinetics is discussed in relation to constant, intermittent, and ramped work rate changes. The influence of heterogeneity in the kinetic matching of O₂ delivery to utilization is presented in reference to exercise tolerance in endurance-trained athletes, the elderly, and patients with chronic heart or lung disease.

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Linking Pulmonary Oxygen Uptake, Muscle Oxygen Utilization and Cellular Metabolism during Exercise

Cited by 23 publications

References 67 publications

Models of muscle contraction and energetics

Models of muscle contraction and energetics

Non-Invasive Estimation Of Metabolic Flux And Blood Flow In Working Muscle: Effect Of Blood-Tissue Distribution

Exercise: Kinetic Considerations for Gas Exchange

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