Takafumi Hamaoka, MD, PhDFaculty of Sport and Health Science,Ritsumeikan University,Kyoto, JAPAN

MUSCLE RESEARCH WORK WITH BRITTON CHANCE FROM IN VIVO MAGNETIC RESONANCE SPECTROSCOPY TO NEAR-INFRARED SPECTROSCOPY

Takafumi Hamaoka, MD, PhD

Kevin K. McCully, PhDUniversity of Georgia

The first point of contact between BC

The first point of contact between BC

• The first point of contact between BC and our research group was in late 1980’s in Hawaii Triathlon Race (Hawaii is a good place to visit as a vacation, but not as a field research, HOT!!).

Prof. Iwane

The first point of contact between BC

• I have heard that Prof. Iwane, my former supervisor in cardiology, had met one (presumably Dr. Pamela Douglas) of the cardiologists travelled from U of Penn to Hawaii, who had told BC a phenomenon of myoglobinemia (>103 fold post-race) after triathlon race lasting over 10 hours.

• Then, BC invited Iwane, who did not conducted basic science, but rather inclined to clinical science, to his lab and had him talk about long-distance race and myoglobinemia. Inviting Iwane was puzzling to us (and also himself) at that time.

• But, I have understood why BC had contacted Iwane, later at a table over a dinner with BC. We have already chased and tested exhaustive triathletes immediately after the race for changes in near-infrared myoglobin and hemoglobin signals using off-line mini-RunMan with a battery for a field study which Chris Albani had built. (I have even heard that BC wanted to ship a magnet from Japan to Philadelphia and temporarily install the magnet in Hawaii on the way for testing exhaustive muscle of triathletes!!)

• BC was trying to calculate on a napkin how much intramuscular myoglobin was released to the blood stream and urine over the race based on Iwane’s research data. The amount of Mb, which has been released to extramuscular space, would correspond to the decrease in muscle NIR signal post-race. In a melting human muscle model, BC wanted to differentiate Mb signal from overall NIR signals which, I believe, still remains to be solved.

Conventional Muscle Study

Muscle biopsy

Happy with muscle biopsy?

METHODOLOGIES

Tc

MRS

NIRS

MRI

US

φ

L

Mus

cle V

O2 (f

old of

resti

ng)

・

Muscle Cell

Oxidative Metabolism

ADP, Pi PCr

NAD/NADHMotor Nerve

Ach.

Muscle Pump

Symp. Nerve

Metabolites

O2

Cardiac Output

N.A.

NOActive Muscle

Contraction

Viscera

Brain ?

?

NOHbO2

Non-active Limbs

Temperature

Noninvasive Measures of Muscle Metabolism and Circulation

ATP

N.A.

VO2.Mit.

Blood FlowVO2.

Blood Flow

VO2.

+

-

+ ++

+

+

-

-

-

Less Active Organs

NIRS

Doppler

MRS

Respr. Gas Analysis

Control of Oxidative Metabolism 1. Kinetic Control by ADP (Chance : Proc.Natl.Acad.Sci., 1985)

[ADP]=([ATP]/[PCr])[Creatine] / (Kck

[H+])

Steady-State condition proposed by B. Chance

ATP, [H +]=Constant, Creatine=Pi

then, [Pi] / [PCr] = [ADP] Kck

[H+] / [ATP]

[Pi] / [PCr]= K'[ADP]

2. Thermodynamic Control (Meyer : Am. J. Physiol., 1988)

Δ GATP

=Δ G0ATP

- RTlog([ATP]=([ADP]/[Pi])

Δ GATP

=K- k[PCr] 20%of Tc <PCr < 75% of Tc

What stimulates mitochondrial oxygen consumption?

Time (sec)

84072060048036024012000

26

27

28

29

30

31

32

0

20

40

60

80

100

PC

r (m

M)

m-O

2 (

% o

f re

sti

ng

)

Arterial Occlusion

Changes in Muscle PCr and HbO2 during Resting Arterial Occlusion

BMR NMR

VO2 REST NIR

Hamaoka et al., JAP, 1996

0

20

40

60

80

100PvO2

PintO2

Time (min)

PO

2 (T

orr)

242220181614121086420

Arterial Occlusion

Fig. 3. Changes in muscle interstitial PO2 (PintO2) and venous PO2 (PvO2)

during resting arterial occlusion.

Hamaoka et al., J. Biomed. Opt., 2000

There is no oxygen gradient betweenvenous and interstitial compartments

Functional anoxic condition

Basal metabolic rate measurement

= 8.2 M ATP/sec

m-O

2 (%

of

res

tin

g)

141210864200

20406080

100

GripArterial Occlusion

Arterial Occlusion

S1 S2

Time (min)

VO2 REST NIR VO2 EX

NIR

1211109876543210

95

100

Time (sec)

m-O

2 (%

of

rest

ing) R^2 = 0.971

75

40

45

50

55

60

65

70

R^2 = 0.980

Post-Exercise

Resting

Arterial Occlusion

S1

S2 End of Exercise

= 8.2 M ATP/sec

= 82 M ATP/sec

x 10

Four different intensities of exercisefor changes in both muscle oxygen consumptionand phosphorus metabolites

50454035302520150

2

4

6

8

10

12

ADP ( µM)

O2 C

onsu

mpt

ion

(µM

O2/s

ec)

y = - 6.6752 + 0.43421x R^2 = 0.989

Relation between VO2 measured by NIRS and ADP measured by MRS

J. Appl. Physiol. Hamaoka et al.1996

3230282624222020

0

2

4

6

8

10

12

PCr (mM)

y = 30.016 - 0.90554x R^2 = 0.993

O2

Con

sum

ptio

n (µ

MO

2/se

c)

Relation between VO2 measured by NIRS and PCr measured by MRS

J. Appl. Physiol. Hamaoka et al.

Display and self-powered sensor

NIRS imager with display

Energy harvesting

sensor

flexible display

energy harvesting module,data logging module

sunlight or LED

Flexible display

3) What is the major challenge to achieving this?

Summary

BC has conducted MRS and NIRS research on elite athletes and a number of chronic health conditions, including patients with chronic heart failure, peripheral vascular disease, and neuromuscular myopathies.

As MRS and NIRS technologies are practical and useful for measuring human muscle metabolism, we will strive to continue Chance’s legacy by advancing muscle MRS and NIRS studies.

BC,

thank you for your time for us!!

Triathlete100km Runner

TennisPlayer

Middle Aged

Faculty of Sport and Health Science,Ritsumeikan University,Kyoto, JAPAN