Mitochondrial function and oxygen supply in normal and in chronically ischemic muscle: a combined 31P magnetic resonance spectroscopy and near infrared spectroscopy study in vivo.
OBJECTIVE
We used (31)P magnetic resonance spectroscopy (MRS) and near-infrared spectroscopy (NIRS) as a means of quantifying abnormalities in calf muscle oxygenation and adenosine triphosphate (ATP) turnover in peripheral vascular disease (PVD).


METHODS
Eleven male patients with PVD (mean age, 65 years; range, 55-76 years) and nine male control subjects of similar age were observed in a case-control study in vascular outpatients. Inclusion criteria were more than 6 months' calf claudication (median, 1.5 years; range, 0.6-18 years); proven femoropopliteal or iliofemoral occlusive or stenotic disease; maximum treadmill walking distance (2 km/h, 10 degrees gradient) of 50 to 230 m (mean, 112 m); ankle-brachial pressure index of 0.8 or less during exercise (mean, 0.47; range, 0.29-0.60). Exclusion criteria included diabetes mellitus, anemia, and magnet contraindications. Simultaneous (31)P MRS and NIRS of lateral gastrocnemius was conducted during 2 to 4 minutes of voluntary 0.5 Hz isometric plantarflexion at 50% and 75% maximum voluntary contraction force (MVC), followed by 5 minutes recovery. Each subject was studied three times, and the results were combined.


RESULTS
Compared with control subjects, patients with PVD showed (1) normal muscle cross-sectional area, MVC, ATP turnover, and contractile efficiency (ATP turnover per force/area); (2) larger phosphocreatine (PCr) changes during exercise (ie, increased shortfall of oxidative ATP synthesis) and slower PCr recovery (47% +/- 7% [mean +/- SEM] decrease in functional capacity for oxidative ATP synthesis, P = .001); (3) faster deoxygenation during exercise and slower postexercise reoxygenation (59% +/- 7% decrease in rate constant, P = .0009), despite reduced oxidative ATP synthesis; (4) correlation between PCr and NIRS recovery rate constants (P < .02); and (5) correlations between smaller walking distance, slower PCr recovery, and reduced MVC (P < .001). The precision of the key measurements (rate constants and contractile efficiency) was 12% to 18% interstudy and 30% to 40% intersubject.


CONCLUSIONS
The primary lesion in oxygen supply dominates muscle metabolism. Reduced force-generation in patients who are affected more may protect muscle from metabolic stress.
Kemp
G J
GJ
Department of Musculoskeletal Science, University of Liverpool, UK. gkemp@liv.ac.uk
Roberts
N
N
Bimson
W E
WE
Bakran
A
A
Harris
P L
PL
Gilling-Smith
G L
GL
Brennan
J
J
Rankin
A
A
Frostick
S P
SP
D000255:Adenosine Triphosphate / Q000378:metabolism; D000368:Aged; D016022:Case-Control Studies; D002908:Chronic Disease; D004734:Energy Metabolism; D005080:Exercise Test; D006801:Humans; D007383:Intermittent Claudication / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology* / Q000628:therapy; D007511:Ischemia / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology* / Q000628:therapy; D007537:Isometric Contraction / Q000502:physiology; D007866:Leg / Q000098:blood supply*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000502:physiology*; D018482:Muscle, Skeletal / Q000098:blood supply*; D010101:Oxygen Consumption / Q000502:physiology*; D016491:Peripheral Vascular Diseases / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology* / Q000628:therapy; D012720:Severity of Illness Index; D019265:Spectroscopy, Near-Infrared; D016138:Walking
D000255:Adenosine Triphosphate