MODULATION OF ATP PRODUCTION BY OXYGEN IN OBSTRUCTIVE LUNG-DISEASE ASASSESSED BY P-31-MRS

Inadequate O-2 supply may impair intramuscular oxidative metabolism an d O-2 availability may modulate ATP production within exercising muscl e. Therefore, we studied ATP flux from anaerobic glycolysis, the creat ine kinase reaction, and oxidative phosphorylation using P-31-magnetic resonance spectroscopy kinetic data collected during exercise. We exa mined six chronic obstructive pulmonary disease (COPD) patients with s evere hypoxemia (group 1), seven COPD patients with mild hypoxemia (gr oup 2), and seven healthy control subjects. Exercise (90-s isometric c ontraction of the gastrocnemius-soleus muscle group, 40% of max) was p erformed on room air for all subjects; for COPD patients, it was repea ted during supplemental O-2 at identical power outputs, with 60-min re st between the two sets. In group 1 (air vs. O-2), oxidative phosphory lation ATP production was lower (P < 0.05), anaerobic glycolysis ATP p roduction was higher (P < 0.05), and anaerobic glycolysis plus creatin e kinase ATP production tended to be higher (P = 0.06). In group 2, no differences were observed across conditions. Assuming that mitochondr ial size, density, function, and redox state were not affected by acut e changes in the inspired O-2 fraction, reduced O-2 availability is th e remaining factor that could have limited oxidative ATP production du ring hypoxemia. In conclusion, in severely hypoxemic COPD patients, O- 2 availability apparently limits intramuscular oxidative metabolism be cause acute hypoxemia increases anaerobic and decreases aerobic ATP pr oduction.