Premium
Quantitative analysis of oxygen transport and cellular metabolism in working skeletal muscle
Author(s) -
Lai Nicola,
Spires Jessica,
Grassi Bruno,
Gladden L Bruce,
Saidel Gerald
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.1065.7
Subject(s) - skeletal muscle , anaerobic exercise , oxygen transport , work rate , chemistry , glycolysis , metabolism , biophysics , homeostasis , myocyte , muscle contraction , oxygen , medicine , biochemistry , endocrinology , biology , physiology , heart rate , blood pressure , organic chemistry
Oxygen uptake dynamics of skeletal muscle (VO 2m ) in response to exercise slow with aging and disease states. Whether O 2 delivery or metabolic changes are limiting the VO 2m response has not been quantitatively distinguished. Previous humans studies found that intracellular O 2 (iPO 2 ) reached a plateau at 60% of the maximal work rate, while another study found iPO 2 linearly related to work rate. Based on these apparent contradictory results, there are alternative hypotheses relating muscle work rate to O 2 diffusion rate from capillary to myocytes. In this study, mechanisms regulating VO 2m response to muscle contraction were analyzed by computational modeling and simulation of experimental data. A mechanistic mathematical model was developed to simulate O 2 transport and cellular metabolism in skeletal muscle. The metabolic processes include anaerobic glycolysis, which plays an important role in ATP homeostasis at higher intensity exercise. The model was validated by comparison of simulated outputs to VO 2m dynamics from canine muscle electrically stimulated in situ under various conditions (O 2 content, blood flow, and stimulus intensity) to mimic human exercise. This model quantitatively related iPO 2 changes to increases of ATP demand under different experimental conditions. This analysis suggests that VO 2m response to high intensity exercise is limited by O 2 diffusion rather than metabolic processes. Research Support: NIH‐NIDDK, GM088823‐012 and NASA, NNJ06HD81G.