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Am. J. Respir. Crit. Care Med., Volume 160, Number 6, December 1999, 1994-1999

Cerebral Bioenergetics in Stable Chronic Obstructive Pulmonary Disease

RAJAT MATHUR, I. JANE COX, ANGELA OATRIDGE, DANIEL T. SHEPHARD, RORY J. SHAW, and SIMON D. TAYLOR-ROBINSON

Department of Medicine, Imperial College School of Medicine, London; Department of Imaging, Division of Investigative Science, Imperial College School of Medicine, London; and Clinical Sciences Centre, Robert Steiner Magnetic Resonance Unit, Hammersmith Hospital, London, United Kingdom

Cerebral intracellular energy production (cerebral bioenergetics) via oxidative phosphorylation and the production of adenosine triphosphate (ATP) is critical to cerebral function. To test the hypothesis that patients with chronic stable hypoxia also generate neuronal ATP via an anaerobic metabolism, we studied the changes in cerebral 31P magnetic resonance spectra (31P 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 COPD (age: 65 ± 9 yr [mean ± SD]; PaO2: 8.8 ± 1.2 kPa; PaCO2: 6.1 ± 0.8 kPa; pH 7.42 ± 0.03, and FEV1: 41 ± 20% predicted) and five healthy volunteers underwent cerebral 31P MRS (TR-5,000 ms) at 1.5 T. When COPD patients were compared with controls, the percentage MR signal with respect to total MR-detectable phosphorus-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 phosphodiesters 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) and of PME to beta ATP (1.0 ± 0.2 versus 0.7 ± 0.1, p = 0.015) were increased, 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 alteration in phosphorus-containing metabolites within cerebral cells provides evidence of extensive use of anaerobic metabolism in hypoxic COPD patients. Mathur R, Cox IJ, Oatridge A, Shephard DT, Shaw RJ, Taylor-Robinson SD. Cerebral bioenergetics in stable chronic obstructive pulmonary disease.




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