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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,

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Presentation on theme: "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,"— Presentation transcript:

1 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

2 OUTLINE: Cardiovascular system or skeletal muscle, who is the boss? Human whole body exercise The middle man, smooth muscle Summary and conclusions Understanding the determinants of maximal exercise model Canine P 50 data Human small muscle mass exercise, intracellular and dilator studies

3 H E A R T M U S C L E S K E L E T A L THE MIDDLE MAN: BLOOD VESSELS

4 H E A R T M U S C L E S K E L E T A L

5 H E A R T M U S C L E S K E L E T A L

6 H E A R T M U S C L E S K E L E T A L

7 H E A R T M U S C L E S K E L E T A L

8 H E A R T M U S C L E S K E L E T A L

9 sGCisGCa GTPcGMP RELAXATION NO Vascular smooth muscle cell Endothelium NOS L-Arginine ENDOTHELIUM / SMOOTH MUSLCE INTERACTION Red blood cell O2O2 ATP NO Heart and lungsSkeletal muscle O2O2

10 HUMAN SINGLE LEG KNEE-EXTENSOR MODEL

11 Blood flow = Qs (Tb2 - Ts) / (Tb1-Tb2)

12 EXERCISE AND ACUTE REDUCTION IN HbO 2

13 BLOOD FLOW AND ACUTE REDUCTION IN HbO 2 :

14 VASOREACTIVITY AND EXERCISE TRAINING

15 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

16 What is VO 2max ?.

17 VO 2max = Q (CaO 2 –CvO 2 ) VO 2max = Ve (FiO 2 –FeO 2 ) VO 2 (l/min) Work rate (Watts) Ve or Q (l/min) Work rate (Watts) Ve Q

18 VO 2 = Q (CaO 2 – CvO 2 )VO 2 = DO 2 (CapPO 2 – CellPO 2 ) DETERMINANTS OF VO 2MAX

19 UNDERSTANDING THE MODEL VO 2 = Q (CaO 2 – CvO 2 ) VO 2 = DO 2 * K * PvO 2

20 UNDERSTANDING THE MODEL CONVECTION DIFFUSION

21 UNDERSTANDING THE MODEL

22 O 2 DELIVERY Q * CaO 2

23 UNDERSTANDING THE MODEL

24 MUSCLE - DIFFUSION LIMITATION? LUNG MUSCLE

25 DEMONSTRATING DIFFUSION LIMITATION

26 CANINE GASTROCNEMIUS PREPARTION

27 CANINE DATA, MANIPULATING P50 Hogan et al. J. Appl. Phys Richardson et al. J. Appl. Phys RSR treated Fall in p50

28 UNDERSTANDING THE MODEL

29 ALTERATIONS IN CONVECTION (DECREASED)

30 ALTERATIONS IN CONVECTION (INCREASED)

31 CHANGES IN BOTH CONVECTION AND DIFFUSION

32 BICYLCE EXERCISE Cardus et al. Med. Sci. Sports Ex Richardson et al. J. Appl. Phys. 1999

33 BICYCLE Vs KNEE-EXTENSOR EXERCISE Richardson et al. J. Appl. Phys. 1999

34 KNEE-EXTENSOR EXERCISE IN THE MRI Richardson et al. J. Clin. Invest. 1995

35 MYOGLOBIN MAGNETIC RESONANCE SPECTROSCOPY Richardson et al. J. Clin. Invest. 1995

36 KNEE-EXTENSOR EXERCISE AND PO 2 Richardson et al. J. Appl. Phys. 1999

37 Untrained Trained II I 50 m Richardson et al. Am. J. Phys. 1999

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39 EXOGENOUS DILATION AT MAXIMAL EXERICSE

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42 SUMMARY AND CONCLUSIONS HIGHLY dependent upon the scenario! O 2 supply limited O 2 demand limited Low capillary density High mitochondrial density Large muscle mass relative to central components Small/unresponsive cardiovascular system relative to peripheral components

43 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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