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![Page 1: Regulation of Mitochondrial Oxygen Consumption at Exercise Onset: O 2 delivery or O 2 utilization? F.W. Kolkhorst Kasch Exercise Physiology Lab San Diego.](https://reader036.fdocuments.us/reader036/viewer/2022062317/5a4d1b3e7f8b9ab05999fd8f/html5/thumbnails/1.jpg)
Regulation of Mitochondrial Oxygen Consumption at Exercise Onset:
O2 delivery or O2 utilization?
F.W. KolkhorstKasch Exercise Physiology Lab
San Diego State University, San Diego, CA
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Why study VO2 kinetics?
Grassi et al., JAP, 1996
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VO2 response to heavy exercise in a representative subject
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0 60 120 180 240 300 360
Time (s)
VO2 (
L·m
in-1
)
Residuals
Kolkhorst et al., MSSE, 2004
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What is primary regulator of mitochondrial respiration at exercise onset?
• Oxygen utilization? (Grassi et al.)
– infers metabolic inertia• Oxygen delivery? (Hughson & Morrisey, JAP, 1982)
– infers that PmitO2 is not saturating in all active muscle fibers at all time points
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Regulation of mitochondrial respiration:O2 utilization (metabolic inertia)?
Peripheral O2 diffusion (capillary-to-mitochondria) as a limiting factor?
• hyperoxic air had no effect on VO2 kinetics (MacDonald et al., JAP 1997)
PO2 in isolated canine muscle had no effect on VO2 kinetics (Grassi et al., JAP 1998)
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VO2 response to electrical stimulation in isolated canine muscle
There were no differences in the time constant between the three conditions. (RSR13 is a drug that shifts O2-Hb dissociation curve to the right) (Grassi et al., JAP 1998)
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O2 deficit during electrical stimulation in isolated canine muscle
Blood flow enhanced with administration of adenosine was compared to control. O2D was ~25% less during enhanced blood flow at high-intensity stimulation (Grassi et al., 1998, 2000).
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Effect of Cr supplementation on VO2 kinetics
• no effect on VO2 response after supplementation (Balsom et al., 1993; Stroud et al.
1994) rapid component amplitude during
exercise >VT after supplementation (Jones et al., 2002)
• faster kinetics after supplementation (Rico-Sands & Mendez-Marco, 2000)
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Placebo Creatine
Pre-treatment
Post-treatment
Pre-treatment
Post-treatment
2 (s) 21.9 8.3 19.2 8.3 28.4 7.9 24.5 7.3
A'2 (Lmin-1) 1.86 0.44 1.89 0.39 1.92 0.48 1.89 0.49
VO2diff6-3 (Lmin-1 ) 2.00 1.52 1.94 1.04 2.28 1.26 2.30 1.24
MRT (s) 65.1 13.2 63.3 12.1
59.8 15.9 62.5 14.0
Shedden et al., unpublished observations
Effect of Cr supplementation on VO2 kinetics during heavy exercise
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O2D in the later bouts was 15% greater after Cr supplementation (P = 0.040)
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Bout
O2 D
efic
it (L
)
Creatine-preCreatine-post
*
Kolkhorst et al., unpublished observations
Effect of Cr supplementation on repeated bouts of supramaximal cycling
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Regulation of mitochondrial respiration:O2 utilization (metabolic inertia)?
Potential mechanisms• Pyruvate dehydrogenase complex (PDH)
– pharmacological intervention spared PCr during exercise transition (Timmons et al., AJP, 1998)
• PCr/Cr– Cr will and PCr will mitochondrial respiration in
vitro (Walsh et al., 2002)• when PCr:Cr was decreased from 2.0 (resting) to 0.5
(low-intensity), small in respiration• when PCr:Cr was further decreased to 0.1 (high-
intensity), large in respiration
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Regulation of mitochondrial respiration:O2 delivery?
Can O2 supply during entire adaptation phase precisely anticipate/exceed O2 demand? (Hughson et al., ESSR, 2001)
– feed forward control from motor cortex/skeletal muscle and CV control center
– matching steady-state O2 delivery requires feedback control mechanisms
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Effects of prior exercise on VO2 kinetics
Light warmup exercise – no affect on VO2 kinetics of subsequent bout
Heavy warmup exercise (Bohnert et al., Exp Physiol, 1998; Gerbino et al., JAP, 1996)
– speeded VO2 kinetics
– metabolic acidosis thought to enhance O2 delivery
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Top: VO2 responses to repeated bouts of supra-LT exercise.
Bottom: VO2 responses to repeated bouts of sub-LT exercise.
Bout 2Bout 1
Gerbino et al., JAP, 1996
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Effects of prior exercise on VO2 kinetics
• later studies suggested that warmup bouts affected only slow component amplitude, not the kinetics (Burnley et al., 2000, 2001)
– used more sophisticated analyses of VO2 kinetics– no effect on rapid component time constant
• breathing hypoxic air slows VO2 kinetics• breathing hyperoxic air speeds VO2 kinetics
at exercise >VT (MacDonald et al., 1997)
– faster MRT, O2D, Phase III amplitude
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HypothesesBicarbonate ingestion would:1. slow rapid component2. decrease magnitude of slow component
PurposeTo investigate effects of bicarbonate ingestion on VO2 kinetics
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Methods
• 10 active subjects (28 9 yr; 82.4 11.2 kg) • On separate days, performed two 6-min bouts
at 25 W greater than VT
– ingested 0.3 gkg-1 body weight of sodium bicarbonate with 1 L of water or water only
• Measured pre-exercise blood pH and [bicarbonate]
• VO2 measured breath-by-breath– used 5-s averages in analysis
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Time (s)
VO2 (
L/m
in)
Raw data
5-s averages
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Three-component model of VO2 kinetics
2
3
1
TD2
A'3
A'2
A'1VO2base
Phase I Phase II
Time
VO2
Initiation of exercise
TD3
Phase III
VO2(t) = VO2base + A1 • (1-e-(t-TD1)/1)+ A2 • (1-e-(t-TD2/2)+ A3 • (1-e-(t-TD3)/3)
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Pre-exercise blood measurements (mean SE)
* P < 0.001
Control trial Bicarbonate trialpH 7.43 0.01 7.51 0.01*
HCO3- (mmol·L-1) 26 1 33 1*
Base excess (mmol·L-1)
2 1 11 1*
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VO2 kinetics from heavy exercise (mean SE)
Control BicarbonateA'2 (mLmin-1) 1444 177 1597 198
TD2 (s) 27.3 3.5 27.2 3.7
2 (s) 20.8 2.4 27.9 3.5*
A'3 (mLmin-1) 649 53 463 43*
TD3 (s) 98.9 11.9 127.5 14.1
3 (s) 244.8 50.5 132.1 21.5
ΔVO2(6-3) (mLmin-1) 302 36 253 40* P < 0.05
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VO2 response to heavy exercise in a representative subject
-0.5
0.0
0.5
1.0
1.5
2.0
2.5
3.0
0 60 120 180 240 300 360
Time (s)
VO2 (
L·m
in-1
)
Residuals
Kolkhorst et al., MSSE, 2004
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Discussion
• Bicarbonate altered manner in which VO2 increased– slower rapid component– smaller slow component
• Why did bicarbonate affect slow component?– bicarbonate attenuates decreases in muscle pH (Nielsen
et al., 2002; Stephens et al., 2002)– Does pH cause fatigue?
• Westerblad et al. (2002) suggested Pi accumulation primary cause
• bicarbonate ingestion performance
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Why did bicarbonate affect rapid component?– alkalosis decreased vasodilation and caused leftward
shift of O2-Hb dissociation curve– effects of prior heavy exercise on rapid component are
equivocal 2 and MRT (MacDonald et al., 1997; Rossiter et al., 2001;
Tordi et al., 2003)• n/c in 2, but A'2 and A'3 (Burnley et al., 2001; Fukuba et al.,
2002)
Why did bicarbonate affect slow component?– bicarbonate attenuates decreases in muscle pH (Nielsen
et al., 2002; Stephens et al., 2002)– Does pH cause fatigue?
• Westerblad et al. (2002) suggested Pi accumulation primary cause
• bicarbonate ingestion performance
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Potential effects of bicarbonate ingestion on slow component
• Slow component may reflect increased motor unit recruitment– fatigue may be due to metabolic acidosis
• Nonsignificant tendencies of smaller ΔVO2(6-3) after bicarbonate ingestion (Santalla et al., 2003; Zoladz et al., 1998)
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Pulmonary VO2 kinetics are known to be:
• faster in trained than untrained• faster during exercise with predominantly ST
fibers than FT fibers• slower after deconditioning• slower in aged population• slower in patients with respiratory/CV
diseases as well as in heart and heart/lung transplant recipients
VO2 kinetics appears to be more sensitive than VO2max or LT to perturbations such as exercise training
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What is primary regulator of mitochondrial respiration at exercise onset?
• Oxygen utilization?• Oxygen delivery?