Regulation of Mitochondrial Oxygen Consumption at Exercise Onset: O2 delivery or O2 utilization

1
Regulation of Mitochondrial Oxygen Consumption at
Exercise OnsetO2 delivery or O2 utilization?

• F.W. Kolkhorst
• Kasch Exercise Physiology Lab
• San Diego State University, San Diego, CA

2
Why study VO2 kinetics?
Grassi et al., JAP, 1996
3
VO2 response to heavy exercise in a
representative subject
Kolkhorst et al., MSSE, 2004
4
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

5
Regulation of mitochondrial respirationO2
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)

6
VO2 response to electrical stimulation in
isolated canine muscleThere 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)
7
O2 deficit during electrical stimulation in
isolated canine muscleBlood 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).
8
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 gtVT
  after supplementation (Jones et al., 2002)
• faster kinetics after supplementation (Rico-Sands
  Mendez-Marco, 2000)

9
Effect of Cr supplementation on VO2 kinetics
during heavy exercise
Shedden et al., unpublished observations
10
O2D in the later bouts was 15 greater after Cr
supplementation (P 0.040)
Effect of Cr supplementation on repeated bouts of
supramaximal cycling

Kolkhorst et al., unpublished observations
11
Regulation of mitochondrial respirationO2
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 PCrCr was decreased from 2.0 (resting) to
  0.5 (low-intensity), small ? in respiration
• when PCrCr was further decreased to 0.1
  (high-intensity), large ? in respiration

12
Regulation of mitochondrial respirationO2
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

13
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

14

Bout 2 Bout 1
Top VO2 responses to repeated bouts of supra-LT
exercise. Bottom VO2 responses to repeated
bouts of sub-LT exercise.
Gerbino et al., JAP, 1996
15
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 gtVT (MacDonald et al., 1997)
• faster MRT, ? O2D, ? Phase III amplitude

16
Purpose To investigate effects of bicarbonate
ingestion on VO2 kinetics

• Hypotheses
• Bicarbonate ingestion would
• slow rapid component
• decrease magnitude of slow component

17
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 g?kg-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

18
(No Transcript)
19
Three-component model of VO2 kinetics
Phase I
Phase II
Phase III
?3
A'3
?2
VO2
A'2
?1
A'1
VO2base
TD2
TD3
Time
Initiation of exercise
VO2(t) VO2base A1 (1-e-(t-TD1)/?1) A2
(1-e-(t-TD2/?2) A3 (1-e-(t-TD3)/?3)
20
Pre-exercise blood measurements (mean ? SE)

P lt 0.001
21
VO2 kinetics from heavy exercise (mean ? SE)
P lt 0.05
22
VO2 response to heavy exercise in a
representative subject
Kolkhorst et al., MSSE, 2004
23
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

24

• 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

25
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 ?VO2(6-3)
  after bicarbonate ingestion (Santalla et al.,
  2003 Zoladz et al., 1998)

26
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
27
What is primary regulator of mitochondrial
respiration at exercise onset?

• Oxygen utilization?
• Oxygen delivery?