OXYGEN SUPPLY AND DEMAND: A MEANS BY WHICH

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OXYGEN SUPPLY AND DEMAND A MEANS BY WHICH TO
INTEGRATE THE OF MUSCLE SYSTEMS
Russell S. Richardson, Ph.D. Department of
Medicine, University of California, San Diego
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OUTLINE

• The middle man, smooth muscle

• Cardiovascular system or skeletal muscle,
• who is the boss?

• Understanding the determinants of
• maximal exercise model

• Canine P50 data

• Human whole body exercise

• Human small muscle mass exercise,
• intracellular and dilator studies

• Summary and conclusions

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THE MIDDLE MAN BLOOD VESSELS
S
M
K
H
U
E
E
S
L
A
C
E
R
L
T
T
E
A
L
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THE MIDDLE MAN BLOOD VESSELS
S
M
K
H
U
E
E
S
L
A
C
E
R
L
T
T
E
A
L
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THE MIDDLE MAN BLOOD VESSELS
S
M
K
H
U
E
E
S
L
A
C
E
R
L
T
T
E
A
L
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THE MIDDLE MAN BLOOD VESSELS
S
M
K
H
U
E
E
S
L
A
C
E
R
L
T
T
E
A
L
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THE MIDDLE MAN BLOOD VESSELS
S
M
K
H
U
E
E
S
L
A
C
E
R
L
T
T
E
A
L
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THE MIDDLE MAN BLOOD VESSELS
S
M
K
H
U
E
E
S
L
A
C
E
R
L
T
T
E
A
L
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ENDOTHELIUM / SMOOTH MUSLCE INTERACTION
Red blood cell
Heart and lungs
Skeletal muscle
O2
ATP
O2
NO
L-Arginine
NOS
Endothelium
NO
sGCi
sGCa
GTP
cGMP
RELAXATION
Vascular smooth muscle cell
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HUMAN SINGLE LEG KNEE-EXTENSOR MODEL
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Blood flow Qs (Tb2 - Ts) / (Tb1-Tb2)
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EXERCISE AND ACUTE REDUCTION IN HbO2
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BLOOD FLOW AND ACUTE REDUCTION IN HbO2
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VASOREACTIVITY AND EXERCISE TRAINING
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QUOTE FROM A RECENT MANUSCRIPT REVIEW
The authors also need to be wary of giving the
supplier (cardiac output) priority over the
consumer (muscle) since the consumer must
drive supply not the other way around (i.e.
increasing supply does not increase demand, but
surely increasing demand requires an increased
supply).
Paper now published Poole et al., Am. J.
Physiol. 284 H1251-H1259, 2003
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.
What is VO2max?
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VO2max Ve (FiO2 FeO2)
VO2max Q (CaO2 CvO2)
Ve
VO2 (l/min)
Ve or Q (l/min)
Q
Work rate (Watts)
Work rate (Watts)
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DETERMINANTS OF VO2MAX
VO2 Q (CaO2 CvO2)
VO2 DO2 (CapPO2 CellPO2)
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UNDERSTANDING THE MODEL
VO2 Q (CaO2 CvO2)
VO2 DO2 K PvO2
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UNDERSTANDING THE MODEL
CONVECTION
DIFFUSION
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UNDERSTANDING THE MODEL
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UNDERSTANDING THE MODEL
O2 DELIVERY Q CaO2
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UNDERSTANDING THE MODEL
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MUSCLE - DIFFUSION LIMITATION?
MUSCLE
LUNG
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DEMONSTRATING DIFFUSION LIMITATION
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CANINE GASTROCNEMIUS PREPARTION
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CANINE DATA, MANIPULATING P50
RSR treated
Fall in p50
Richardson et al. J. Appl. Phys. 1998
Hogan et al. J. Appl. Phys. 1991
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UNDERSTANDING THE MODEL
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ALTERATIONS IN CONVECTION (DECREASED)
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ALTERATIONS IN CONVECTION (INCREASED)
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CHANGES IN BOTH CONVECTION AND DIFFUSION
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BICYLCE EXERCISE
Cardus et al. Med. Sci. Sports Ex. 1998
Richardson et al. J. Appl. Phys. 1999
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BICYCLE Vs KNEE-EXTENSOR EXERCISE
Richardson et al. J. Appl. Phys. 1999
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KNEE-EXTENSOR EXERCISE IN THE MRI
Richardson et al. J. Clin. Invest. 1995
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MYOGLOBIN MAGNETIC RESONANCE SPECTROSCOPY
Richardson et al. J. Clin. Invest. 1995
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KNEE-EXTENSOR EXERCISE AND PO2
Richardson et al. J. Appl. Phys. 1999
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Untrained
I
II
50 ?m
Trained
Richardson et al. Am. J. Phys. 1999
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Richardson et al. Am. J. Phys. 1999
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EXOGENOUS DILATION AT MAXIMAL EXERICSE
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SUMMARY AND CONCLUSIONS

• HIGHLY dependent upon the scenario!

O2 supply limited
Small/unresponsive cardiovascular system relative
to peripheral components
Large muscle mass relative to central components
Low capillary density
High mitochondrial density
O2 demand limited
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Co-workers
Peter Wagner, M.D. Tim Gavin, Ph.D. Odile
Mathieu-Costello, Ph.D. Robert Henry, M.D. Fabio
Esposito, M.D. Harrieth Wagner Elizabeth
Noyszewski, Ph.D. Bryan Leek, M.D. Kuldeep
Tagore, M.D. Sean Newcomer Luke Haseler,
Ph.D. Lawrence Frank, Ph.D. John Leigh,
Ph.D. Eileen Quintela, B.S. Sundar Mudaliar, M.D.
Funding
American Lung Association Parker B. Francis
Foundation National Institute of Health
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