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American Journal of Physiology. Heart... Sep 2006Steady-state metabolite (ADP, ATP, P(i), PCr, and NADH) concentrations usually differ little between different workloads with significantly different oxygen consumption...
Steady-state metabolite (ADP, ATP, P(i), PCr, and NADH) concentrations usually differ little between different workloads with significantly different oxygen consumption rates in the heart. However, during transitions between steady states, metabolite concentrations may in some cases change transiently, exhibiting a significant overshoot or undershoot, whereas in other cases they approach near-exponentially new steady-state values. Oxygen consumption rate usually reaches the new steady-state value very quickly (within a few seconds). The present in silico studies, performed using a previously developed computer model of oxidative phosphorylation in the heart, demonstrate that such a behavior of the oxidative phosphorylation system can be reproduced only under the assumption that ATP usage, substrate dehydrogenation, and (particular steps of) oxidative phosphorylation are directly activated to a similar extend by some cytosolic factor/mechanism during transition from low work to high work (the so-called parallel-activation mechanism). Computer simulations show that some differences observed between different experimental systems can be explained by a slightly different balance of the activation of particular components of the system and/or by a delay in time of the activation/inactivation of substrate dehydrogenation and oxidative phosphorylation during low-to-high and high-to-low work transitions. Thus the presented theoretical approach offers a general idea that is able to unify, at least semiquantitatively, different experimental data available in the literature.
Topics: Adenosine Triphosphate; Animals; Computer Simulation; Energy Metabolism; Heart; Humans; Models, Theoretical; Oxygen Consumption; Phosphorylation
PubMed: 16679405
DOI: 10.1152/ajpheart.00004.2006 -
International Journal of Molecular... Sep 2017Neuronal injury due to seizures may result from a mismatch of energy demand and adenosine triphosphate (ATP) synthesis. However, ATP demand and oxygen consumption rates...
Neuronal injury due to seizures may result from a mismatch of energy demand and adenosine triphosphate (ATP) synthesis. However, ATP demand and oxygen consumption rates have not been accurately determined, yet, for different patterns of epileptic activity, such as interictal and ictal events. We studied interictal-like and seizure-like epileptiform activity induced by the GABA antagonist bicuculline alone, and with co-application of the M-current blocker XE-991, in rat hippocampal slices. Metabolic changes were investigated based on recording partial oxygen pressure, extracellular potassium concentration, and intracellular flavine adenine dinucleotide (FAD) redox potential. Recorded data were used to calculate oxygen consumption and relative ATP consumption rates, cellular ATP depletion, and changes in FAD/FADH₂ ratio by applying a reactive-diffusion and a two compartment metabolic model. Oxygen-consumption rates were ca. five times higher during seizure activity than interictal activity. Additionally, ATP consumption was higher during seizure activity (~94% above control) than interictal activity (~15% above control). Modeling of FAD transients based on partial pressure of oxygen recordings confirmed increased energy demand during both seizure and interictal activity and predicted actual FAD autofluorescence recordings, thereby validating the model. Quantifying metabolic alterations during epileptiform activity has translational relevance as it may help to understand the contribution of energy supply and demand mismatches to seizure-induced injury.
Topics: Action Potentials; Adenosine Triphosphate; Animals; Anthracenes; Bicuculline; Electrophysiology; Flavin-Adenine Dinucleotide; Male; Oxygen Consumption; Rats; Rats, Wistar; Seizures
PubMed: 28880249
DOI: 10.3390/ijms18091925 -
Clinical Cancer Research : An Official... May 2015Tumor hypoxia presents a unique therapeutic challenge in the treatment of solid malignancies. Its presence has been established to be a poor prognostic factor in... (Review)
Review
Tumor hypoxia presents a unique therapeutic challenge in the treatment of solid malignancies. Its presence has been established to be a poor prognostic factor in multiple cancer types, and past hypoxia-directed approaches have yielded generally disappointing results. Previous approaches have centered on either increasing oxygen delivery or administering agents that preferentially radiosensitize or kill hypoxic cells. However, a novel and potentially more effective method may be to increase therapeutic benefit by decreasing tumor oxygen consumption via agents such as metformin or nelfinavir in a patient population that is enriched for tumor hypoxia. This promising approach is currently being investigated in clinical trials and the subject of this article.
Topics: Cell Hypoxia; Humans; Neoplasms; Oxygen Consumption; Radiation-Sensitizing Agents
PubMed: 25934887
DOI: 10.1158/1078-0432.CCR-14-0858 -
Journal of Applied Physiology... Dec 2014
Topics: Animals; Hypoxia; Male; Oxygen Consumption; Respiration
PubMed: 25512069
DOI: 10.1152/japplphysiol.00893.2014 -
Critical Care (London, England) 2010This article is one of ten reviews selected from the (Springer Verlag) and co-published as a series in . Other articles in the series can be found online at... (Review)
Review
This article is one of ten reviews selected from the (Springer Verlag) and co-published as a series in . Other articles in the series can be found online at http://ccforum.com/series/yearbook. Further information about the is available from http://www.springer.com/series/2855.
Topics: Blood Transfusion; Catheterization, Central Venous; Decision Making; Humans; Monitoring, Physiologic; Oxygen; Oxygen Consumption
PubMed: 20236457
DOI: 10.1186/cc8854 -
STAR Protocols Sep 2020Analysis of mitochondrial respiration function represented by the oxygen consumption rate is necessary for assessing mitochondrial respiration function. This protocol...
Analysis of mitochondrial respiration function represented by the oxygen consumption rate is necessary for assessing mitochondrial respiration function. This protocol describes steps to evaluate the respiration function of mitochondria in saponin-permeabilized cardiomyocytes. In permeabilized cells, mitochondria are in a relatively integrated cellular system, and mitochondrial respiration is more physiologically relevant than isolated mitochondria. For complete details on the use and execution of this protocol, please refer to Gong et al. (2015a) and Gong et al. (2015b).
Topics: Animals; Cell Membrane Permeability; Cytological Techniques; Myocytes, Cardiac; Oxygen; Oxygen Consumption
PubMed: 33111108
DOI: 10.1016/j.xpro.2020.100072 -
American Journal of Physiology.... Jan 2019During aerobic exercise (>65% of maximum oxygen consumption), the primary source of acetyl-CoA to fuel oxidative ATP synthesis in muscle is the pyruvate dehydrogenase...
During aerobic exercise (>65% of maximum oxygen consumption), the primary source of acetyl-CoA to fuel oxidative ATP synthesis in muscle is the pyruvate dehydrogenase (PDH) reaction. This study investigated how regulation of PDH activity affects muscle energetics by determining whether activation of PDH with dichloroacetate (DCA) alters the dynamics of the phosphate potential of rat gastrocnemius muscle during contraction. Twitch contractions were induced in vivo over a broad range of intensities to sample submaximal and maximal aerobic workloads. Muscle phosphorus metabolites were measured in vivo before and after DCA treatment by phosphorus nuclear magnetic resonance spectroscopy. At rest, DCA increased PDH activation compared with control (90 ± 12% vs. 23 ± 3%, P < 0.05), with parallel decreases in inorganic phosphate (P) of 17% (1.4 ± 0.2 vs. 1.7 ± 0.1 mM, P < 0.05) and an increase in the free energy of ATP hydrolysis (ΔG) (-66.2 ± 0.3 vs. -65.6 ± 0.2 kJ/mol, P < 0.05). During stimulation DCA increased steady-state phosphocreatine (PCr) and the magnitude of ΔG, with concomitant reduction in P and ADP concentrations. These effects were not due to kinetic alterations in PCr hydrolysis, resynthesis, or glycolytic ATP production and altered the flow-force relationship between mitochondrial ATP synthesis rate and ΔG. DCA had no significant effect at 1.0- to 2.0-Hz stimulation because physiological mechanisms at these high stimulation levels cause maximal activation of PDH. These data support a role of PDH activation in the regulation of the energetic steady state by altering the phosphate potential (ΔG) at rest and during contraction.
Topics: Adenosine Triphosphate; Animals; Energy Metabolism; Male; Muscle Contraction; Muscle, Skeletal; Oxidation-Reduction; Oxidoreductases; Oxygen Consumption; Pyruvate Dehydrogenase Complex; Rats, Wistar
PubMed: 30462525
DOI: 10.1152/ajpregu.00321.2018 -
European Journal of Heart Failure Aug 2007Patients with chronic heart failure (CHF) have a lower peak oxygen consumption (pVO2) than normal subjects, and for a given quantity of work, have a lower total oxygen...
INTRODUCTION
Patients with chronic heart failure (CHF) have a lower peak oxygen consumption (pVO2) than normal subjects, and for a given quantity of work, have a lower total oxygen consumption (VO2) than controls. This apparent increase in biomechanical efficiency (BE) might be due to a higher proportion of anaerobic metabolism which, although leading to lower VO2 during steady state exercise, must be compensated for during recovery.
METHODS
13 patients with stable CHF and 12 controls underwent peak cycle exercise testing followed by three separate steady state exercise tests at 15%, 25% and 50% of the peak workload in random order. Oxygen consumption at steady state, deficit (during onset) and debt (during recovery) were calculated. BE was estimated as the total oxygen required to perform a given quantity of work.
RESULTS
Patients had lower pVO2 and peak workload than control subjects. Absolute oxygen deficit and debt as a percentage of total oxygen consumed during the steady state tests was the same in both groups. However, once controlled for workload, VO2 deficit, debt and uptake at steady state were greater in patients than controls for the tests at 15% and 25% of peak. BE was inversely related to peak oxygen consumption in controls and patients.
CONCLUSIONS
Patients with CHF have impaired BE at low work loads when compared with normal subjects.
Topics: Aged; Anaerobic Threshold; Biomechanical Phenomena; Energy Metabolism; Exercise; Heart Failure; Humans; Male; Middle Aged; Muscle, Skeletal; Oxygen Consumption
PubMed: 17569581
DOI: 10.1016/j.ejheart.2007.05.004 -
Nutrients Apr 2019Intramyocellular (IMCL), extramyocellular lipid (EMCL), and vitamin D deficiency are associated with muscle metabolic dysfunction. This study compared the change in... (Randomized Controlled Trial)
Randomized Controlled Trial
Intramyocellular (IMCL), extramyocellular lipid (EMCL), and vitamin D deficiency are associated with muscle metabolic dysfunction. This study compared the change in [IMCL]:[EMCL] following the combined treatment of vitamin D and aerobic training (DAT) compared with vitamin D (D), aerobic training (AT), and control (CTL). Male and female subjects aged 60-80 years with a BMI ranging from 18.5-34.9 and vitamin D status of ≤32 ng/mL (25(OH)D) were recruited to randomized, prospective clinical trial double-blinded for supplement with a 2 × 2 factorial design. Cholecalciferol (Vitamin D) (10,000 IU × 5 days/week) or placebo was provided for 13 weeks and treadmill aerobic training during week 13. Gastrocnemius IMCL and EMCL were measured with magnetic resonance spectroscopy (MRS) and MRI. Hybrid near-infrared diffuse correlation spectroscopy measured hemodynamics. Group differences in IMCL were observed when controlling for baseline IMCL ( = 0.049). DAT was the only group to reduce IMCL from baseline, while a mean increase was observed in all other groups combined ( = 0.008). IMCL reduction and the corresponding increase in rVO at study end ( = 0.011) were unique to DAT. Vitamin D, when combined with exercise, may potentiate the metabolic benefits of exercise by reducing IMCL and increasing tissue-level VO in healthy, older adults.
Topics: Aged; Dietary Supplements; Exercise; Female; Humans; Lipid Metabolism; Male; Middle Aged; Muscle, Skeletal; Oxygen Consumption; Vitamin D
PubMed: 31027191
DOI: 10.3390/nu11040930 -
International Journal of Sports Medicine May 2022In 1973 Wasserman, Whipp, Koyal, and Beaver published a groundbreaking study titled "Anaerobic threshold and respiratory gas analysis during exercise". At that time,...
In 1973 Wasserman, Whipp, Koyal, and Beaver published a groundbreaking study titled "Anaerobic threshold and respiratory gas analysis during exercise". At that time, respiratory gas analysis and laboratory computers had evolved such that more advanced respiratory exercise physiology studies were possible. The initial publications from this group on the onset of anaerobic metabolism in cardiac patients, the first breath-by-breath VO system, the first description of the anaerobic threshold, and then later new methods to detect the anaerobic threshold have been and continue to be highly cited. In fact, their 1973 anaerobic threshold paper is the sixth and their 1986 paper is the second most cited paper ever published in the Journal of Applied Physiology. The anaerobic threshold concept has also generated>5500 publications with the rates increasing over time. The publication of two papers that help to refute the "anaerobic" explanation for this phenomenon had no effect on the rates of citations of the original anaerobic threshold papers or the number of anaerobic threshold papers published since. Thus, despite now substantial evidence refuting the proposed anaerobic mechanisms underlying this phenomenon, these papers continue to be highly influential in the discipline of exercise physiology and, perhaps even more explicitly, clinical exercise physiology.
Topics: Anaerobic Threshold; Anaerobiosis; Exercise; Exercise Test; Humans; Oxygen Consumption
PubMed: 34879397
DOI: 10.1055/a-1664-8854