Am. J. Respir. Crit. Care Med., Volume 157, Number 2, February 1998, 453-457

Elevated Inosine Monophosphate Levels in Resting Muscle of Patients with Stable Chronic Obstructive Pulmonary Disease

ELLEN M. POUW, ANNEMIE M. W. J. SCHOLS, GER J. van der VUSSE, and EMIEL F. M. WOUTERS

Departments of Pulmonology and Physiology, Maastricht University, Maastricht; and Asthmacentre Hornerheide, Horn, The Netherlands

In order to investigate disturbances in energy metabolism in resting muscle of patients with stable chronic obstructive pulmonary disease (COPD), concentrations of adenine nucleotides and related compounds were examined comparing 34 COPD patients with eight age-matched healthy control subjects. Biopsies were taken from the anterior tibialis muscle. Special attention was paid to the muscle content of inosine monophosphate (IMP), a deamination product of adenosine monophosphate (AMP), because IMP formation is thought to reflect an imbalance between resynthesis and utilization of adenosine triphosphate (ATP). The absolute concentrations of high-energy phosphate compounds did not differ between patients and control subjects, but the ATP/ADP and the phosphocreatine/creatine ratio were significantly lower in the patients. IMP (detection level = 0.06 mmol/kg dry weight) was detected in 25 of 34 patients versus one of eight control subjects (p = 0.001). Mean (SD) IMP level in these patients was 0.18 (0.14) versus 0.06 mmol/kg dry weight in the one control subject. Based on the presence of detectable levels of muscle IMP, the patient group was divided into two subgroups. In IMP-positive patients, ATP/ADP and phosphocreatine/creatine ratios were significantly lower than in IMP-negative patients. IMP-positive patients were furthermore characterized by a significantly lower DL_CO. The results of this study indicate an imbalance between the utilization and resynthesis of ATP in resting muscle of patients with stable COPD.

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