MUSCLE RESEARCH WORK WITH BRITTON CHANCE
FROM IN VIVO MAGNETIC RESONANCE
SPECTROSCOPY TO NEAR-INFRARED SPECTROSCOPY
Takafumi Hamaoka, MD, PhD
Kevin K. McCully, PhD
University of Georgia
Takafumi Hamaoka, MD, PhD
Faculty of Sport and Health Science,
Ritsumeikan University,
Kyoto, JAPAN
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
MRI
・
L
Muscle VO2 (fold of resting)
NIRS
US
φ
Noninvasive Measures of Muscle
Metabolism and Circulation
Muscle Cell
MRS
Oxidative
Metabolism
Mit.
ADP, Pi
NIRS
Contraction
Ach.
ATP
.
VO2
?
PCr
+
Active HbO2
NO
Muscle
Less Active
Organs
Viscera
Non-active
Limbs
Brain ?
Respr. Gas
Analysis
Metabolites
O2
Cardiac
Output
Doppler
-
+
Temperature
+
Motor Nerve
NAD/NADH
+
Muscle Pump
NO
N.A.
-
+
N.A.
.
VO2
Blood Flow
.
Symp. Nerve
-
VO2
Blood Flow
+
What stimulates mitochondrial oxygen
consumption?
Control of Oxidative Metabolism
1. Kinetic Control by ADP (Chance : Proc.Natl.Acad.Sci., 1985)
[ADP]=([ATP]/[PCr])[Creatine] / (K ck[H+])
Steady-State condition proposed by B. Chance
ATP, [H+]=Constant, Creatine=Pi
then, [Pi] / [PCr] = [ADP] K ck[H+] / [ATP]
[Pi] / [PCr]= K'[ADP]
2. Thermodynamic Control (Meyer : Am. J. Physiol., 1988)
ΔGATP=ΔG0ATP- RTlog([ATP]=([ADP]/[Pi])
ΔGATP=K- k[PCr]
20%of Tc <PCr < 75% of Tc
Basal metabolic
rate
Changes
in Muscle PCr
and HbO2
during
Resting Arterial Occlusion
measurement
BMR NMR
30
PO2 (Torr)
31
PCr (mM)
PvO2
Pint O2
80
32
m-O 2 (% of resting)
100
60
40
29
20
28
0
= 8.2 mM ATP/sec
27
26
Arterial Occlusion
0
2
4
6
8 10 12 14 16 18 20 22 24
Time (min)
100
Fig. 3. Changes in muscle interstitial PO
80
VO2 REST NIR
60
2
(PintO2) and venous PO2 (PvO2)
during resting arterial occlusion.
Hamaoka et al., J. Biomed. Opt., 2000
40
20
0
Arterial Occlusion
0
120 240
Hamaoka et al., JAP, 1996
360 480 600 720 840
Time (sec)
There is no oxygen gradient between
venous and interstitial compartments
Functional anoxic condition
m-O2 (% of resting)　Arterial
Occlusion Grip
100
80
60
40
20
0
S2
S1
VO2 REST NIR
0 2 4
Arterial
Occlusion
VO2 EX NIR
6 8 10 12 14
Time (min)
m-O2 (% of resting)
100
R^2 = 0.971
95
S1
= 8.2 mM ATP/sec
75
x 10
70
R^2 = 0.980
65
60
S2
= 82 mM ATP/sec
55
Resting
PostEnd of
Exercise
Exercise
50
45
40
Arterial Occlusion
0
1
2 3
4
5 6 7 8
Time (sec)
9 10 11 12
Four different intensities of exercise
for changes in both muscle oxygen consumption
and phosphorus metabolites
Relation between VO2 measured by
NIRS and ADP measured by MRS
O 2 Consumption (µMO 2/sec)
y = - 6.6752 + 0.43421x R^2 = 0.989
12
10
8
6
4
2
0
15
20
25
30
35
ADP ( µM)
40
45
50
J. Appl. Physiol. Hamaoka et al.
1996
O2 Consumption (µMO2/sec)
Relation between VO 2 measured by
NIRS and PCr measured by MRS
12
y = 30.016 - 0.90554x R^2 = 0.993
10
8
6
4
2
0
20
22
24
26
28
30
32
PCr (mM)
J. Appl. Physiol. Hamaoka et al.
NIRS imager with display
3) What is the major
challenge to achieving this?
Display and self-powered sensor
Energy harvesting
Flexible display
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!!
Middle
Aged
100km Triathlete
Runner
Tennis
Player
Faculty of Sport and
Health Science,
Ritsumeikan University,
Kyoto, JAPAN