Cerebral bioenergetics in stable chronic obstructive pulmonary disease

Cerebral intracellular energy production (cerebral bioenergetics) via oxida tive phosphorylation and the production of adenosine triphosphate (ATP) is critical to cerebral function. To test the hypothesis that patients with ch ronic stable hypoxia also generate neuronal ATP via an anaerobic metabolism , we studied the changes in cerebral P-31 magnetic resonance spectra (P-31 MRS) in patients with stable chronic obstructive pulmonary disease (COPD), and compared the results with MR spectra from similar areas of the brain in control subjects. Ten patients with stable CORD (age: 65 +/- 9 yr [mean +/ - SD]; Pa-O2 : 8.8 +/- 1.2 kPa; Pa-CO2 : 6.1 +/- 0.8 kPa; pH 7.42 +/- 0.03, and FEV1 : 41 +/- 20% predicted) and five healthy volunteers underwent cer ebral P-31 MRS (TR-5,000 ms) at 1.5 T. When COPD patients were compared wit h controls, the percentage MR signal with respect to total MR-detectable ph osphorus-containing metabolites was increased from inorganic phosphate (Pi) (7.1 +/- 1.3% versus 3.9 +/- 0.7%, p = 0.0001) and phosphomonoesters (PMEs ) (9.4 +/- 1.2% versus 6.9 +/- 0.3%, p = 0.0001), whereas the signal from p hosphodiesters was reduced (34.8 +/- 3.2 versus 40.4 +/- 3.3%, p = 0.015). The ratios of Pi to beta ATP (0.8 +/- 0.2 versus 0.4 +/- 0.1, p = 0.001) an d of PME to beta ATP (1.0 +/- 0.2 versus 0.7 +/- 0.1, p = 0.015) were incre ased, but the phosphocreatine-to-Pi ratio (2.1 +/- 0.6 versus 3.2 +/- 0.6, p = 0.01) was reduced in patients as compared with controls. This alteratio n in phosphorus-containing metabolites within cerebral cells provides evide nce of extensive use of anaerobic metabolism in hypoxic COPD patients.