Dissociation of maximal O2 uptake from O2 delivery in canine gastrocnemius in situ

Hogan, Michael C.; Roca, Josep; West, J. B.; Wagner, Peter D.

doi:10.1152/jappl.1989.66.3.1219

Cited by 82 publications

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“…5 B, Table I). This single level of diffusional conductance at WRMAX is consistent with other studies (8,30,31) and the theory that diffusion limitation may play a role in determining V02mx,, in exercising muscle (4).…”

Section: Discussionsupporting

confidence: 91%

“…Based on direct measurements of intracellular Po2 (28) and mathematical modeling (29) in maximally exercising muscle, previous analyses of diffusivity, not knowing PMITOO2, have limited their calculations to Vo2n,, where it was assumed cellular Po2 was very low ( 1-3 mmHg range) and so could be neglected (4,6,30,31). The present study has demonstrated that the assumption of a low intracellular P02 at V02m,., relied upon in these initial investigations, was valid and in fact is the case even at submaximal exercise intensities eliciting only 50% of VO2max (Fig.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Myoglobin O2 desaturation during exercise. Evidence of limited O2 transport.

Richardson¹,

Noyszewski²,

Kendrick³

et al. 1995

J. Clin. Invest.

550

527

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Myoglobin O2 desaturation during exercise. Evidence of limited O2 transport.

Richardson¹,

Noyszewski²,

Kendrick³

et al. 1995

J. Clin. Invest.

550

527

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“…These simulations explain quantitatively how O 2 diffusion may limit muscle oxidative metabolism at maximal contraction rate, as suggested from canine muscle data (25,29). However, at submaximal contraction, V O 2 on-kinetics are not affected by arterial O 2 content, implying the absence of O 2 diffusion limitation (24).…”

Section: Relationship Between Ipo 2 and Energy Demandsupporting

confidence: 60%

Model analysis of the relationship between intracellular Po₂and energy demand in skeletal muscle

Spires

Gladden

Grassi

et al. 2012

American Journal of Physiology-Regulatory, Integrative and Comp

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Spires J, Gladden LB, Grassi B, Saidel GM, Lai N. Model analysis of the relationship between intracellular PO2 and energy demand in skeletal muscle. Am J Physiol Regul Integr Comp Physiol 303: R1110 -R1126, 2012. First published September 12, 2012 doi:10.1152/ajpregu.00106.2012.-On the basis of experimental studies, the intracellular O2 (iPO2)-work rate (WR) relationship in skeletal muscle is not unique. One study found that iPO2 reached a plateau at 60% of maximal WR, while another found that iPO2 decreased linearly at higher WR, inferring capillary permeability-surface area (PS) and blood-tissue O2 gradient, respectively, as alternative dominant factors for determining O2 diffusion changes during exercise. This relationship is affected by several factors, including O2 delivery and oxidative and glycolytic capacities of the muscle. In this study, these factors are examined using a mechanistic, mathematical model to analyze experimental data from contracting skeletal muscle and predict the effects of muscle contraction on O2 transport, glycogenolysis, and iPO2. The model describes convection, O2 diffusion, and cellular metabolism, including anaerobic glycogenolysis. Consequently, the model simulates iPO2 in response to muscle contraction under a variety of experimental conditions. The model was validated by comparison of simulations of O2 uptake with corresponding experimental responses of electrically stimulated canine muscle under different O 2 content, blood flow, and contraction intensities. The model allows hypothetical variation of PS, glycogenolytic capacity, and blood flow and predictions of the distinctive effects of these factors on the iPO 2-contraction intensity relationship in canine muscle. Although PS is the main factor regulating O 2 diffusion rate, model simulations indicate that PS and O 2 gradient have essential roles, depending on the specific conditions. Furthermore, the model predicts that different convection and diffusion patterns and metabolic factors may be responsible for different iPO 2-WR relationships in humans. oxygen diffusion; convection; bioenergetics; exercise; glycolysis; contraction THE SKELETAL MUSCLE INTRACELLULAR PO 2 (iPO 2 )-exercise intensity relationship was previously investigated to study the regulatory mechanisms of O 2 consumption (V O 2 ) in working skeletal muscle (49,55,57). In particular, from these NMR studies in humans, skeletal muscle iPO 2 was inferred from measurements of deoxymyoglobin concentration during muscle contraction. The relationships between iPO 2 and metabolic intensity [i.e., work rates (WR)], however, were dissimilar. Molé et al. (49) reported that iPO 2 decreased linearly as WR increased above 50 -60% of peak V O 2 (V O 2peak ), whereas Richardson et al. (55,57) found that iPO 2 was low and constant above 60% of V O 2peak during knee extensor exercise. In addition, Molé et al. inferred that the blood-tissue O 2 gradient, rather than capillary permeability-surface area (PS), as proposed by Richardson et al., was the dominant factor determin...

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“…These effects can decrease RBC transit time thereby minimizing the temporal window for O 2EX (16). The importance of RBC transit time has been reported for both muscle and coronary circulation (24) In our study with Hb of about 3 g/dl at DO 2 CRIT , shortened transit times may be of particular importance because O 2 off-loading kinetics for Hb are two times slower than O 2 loading on Hb (24).…”

Section: Discussionmentioning

confidence: 60%

Increasing P₅₀does not improve Do_2critor systemicV˙o₂in severe anemia

Eichelbrönner

D'Almeida

Sielenkämper

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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binding affinity facilitates O2 unloading from Hb, potentially increasing tissue mitochondrial O2 availability. We hypothesized that a reduction of Hb-O2 affinity would increase O2 extraction when tissues are O2 supply dependent, reducing the threshold of critical O2 delivery (DO2 CRIT). We investigated the effects of increased O2 tension at which Hb is 50% saturated (P50) on systemic O2 uptake (V O2 SYS), DO2 CRIT, lactate production, and acid-base balance during isovolemic hemodilution in conscious rats. After infusion of RSR13, an allosteric modifier of Hb, P 50 increased from 36.6 Ϯ 0.3 to 48.3 Ϯ 0.6 but remained unchanged at 35.4 Ϯ 0.8 mmHg after saline (control, CON). Arterial O 2 saturations were equivalent between RSR13 and saline groups, but venous PO 2 was higher and venous O2 saturation was lower after RSR13. Convective O2 delivery progressively declined during hemodilution reaching the DO2 CRIT at 3.4 Ϯ 0.8 ml ⅐ min Ϫ1 ⅐ 100 g Ϫ1 (CON) and 3.6 Ϯ 0.6 ml ⅐ min Ϫ1 ⅐ 100 g Ϫ1 (RSR13). At Hb of 8.1 g/l V O2 SYS started to decrease (CON: 1.9 Ϯ 0.1; RSR13: 1.8 Ϯ 0.2 ml ⅐ min Ϫ1 ⅐ 100 g Ϫ1 ) and fell to 0.8 Ϯ 0.2 (CON) and 0.7 Ϯ 0.2 ml ⅐ min Ϫ1 ⅐ 100 g Ϫ1 (RSR13). Arterial lactate was lower in RSR13-treated than in control animals when animals were O 2 supply dependent. The decrease in base excess, arterial pH, and bicarbonate during O2 supply dependence was significantly less after RSR13 than after saline. These findings demonstrate that during O 2 supply dependence caused by severe anemia, reducing Hb-O2 binding affinity does not affect V O2 SYS Right shifting the ODC, or increasing the O 2 tension at which Hb is 50% saturated (P 50 ), favors release of O 2 from hemoglobin at higher tissue PO 2 (4, 13). As a consequence, the O 2 gradient between RBCs and the mitochondria is increased, and more of the O 2 transported in the blood is available for consumption in the tissues. This increased O 2 gradient between RBCs and mitochondria should allow O 2 to diffuse over longer distances or offering more O 2 for local mitochondrial metabolism.Recent research has led to the discovery of new allosteric modifiers of the Hb-O 2 affinity (1). RSR13, a 2- [4-[2-[(3,5-dimethylphenyl)amino]-2-oxoethyl]phenoxy]-2-methyl-proprionic acid monosodium salt, reliably reduces the Hb-O 2 affinity in vivo. Because RSR13 binds to a site distinct from that of 2,3-diphosphoglycerate, the naturally occurring allosteric modifier of Hb, RSR13 generates an additive rightward shift of the ODC, which should facilitate added O 2 release (1). Superfusion of tissues with or infusion of RSR13 reduced hypoxia-induced vasodilation (44), increased tissue PO 2 (21), and reduced brain infarct size (43). During maximal exercise, low P 50 diminished maximal O 2 consumption (V O 2 max ) (14), whereas an increased P 50 by RSR13 enhanced maximal O 2 uptake (33). These findings suggest that modifications of the strength of the Hb-O 2 bond can effectively alter tissue O 2 availability.Under normal conditions, tissue O 2 availability and systemic V O 2 (V ...

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Dissociation of maximal O2 uptake from O2 delivery in canine gastrocnemius in situ

Cited by 82 publications

References 0 publications

Myoglobin O2 desaturation during exercise. Evidence of limited O2 transport.

Myoglobin O2 desaturation during exercise. Evidence of limited O2 transport.

Model analysis of the relationship between intracellular Po₂and energy demand in skeletal muscle

Increasing P₅₀does not improve Do_2critor systemicV˙o₂in severe anemia

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Dissociation of maximal O2 uptake from O2 delivery in canine gastrocnemius in situ

Cited by 82 publications

References 0 publications

Myoglobin O2 desaturation during exercise. Evidence of limited O2 transport.

Myoglobin O2 desaturation during exercise. Evidence of limited O2 transport.

Model analysis of the relationship between intracellular Po2and energy demand in skeletal muscle

Increasing P50does not improve Do2critor systemicV˙o2in severe anemia

Contact Info

Product

Resources

About

Model analysis of the relationship between intracellular Po₂and energy demand in skeletal muscle

Increasing P₅₀does not improve Do_2critor systemicV˙o₂in severe anemia