ELEVATED INOSINE MONOPHOSPHATE LEVELS IN RESTING MUSCLE OF PATIENTS WITH STABLE CHRONIC OBSTRUCTIVE PULMONARY-DISEASE

In order to investigate disturbances in energy metabolism in resting m uscle of patients with stable chronic obstructive pulmonary disease (C OPD), concentrations of adenine nucleotides and related compounds were examined comparing 34 COPD patients with eight age-matched healthy co ntrol subjects. Biopsies were taken from the anterior tibialis muscle. Special attention was paid to the muscle content of inosine monophosp hate (IMP), a deamination product of adenosine monophosphate (AMP), be cause IMP formation is thought to reflect an imbalance between resynth esis and utilization of adenosine triphosphate (ATP). The absolute con centrations 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 (detecti on 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 th e one control subject. Based on the presence of detectable levels of m uscle IMP, the patient group was divided into two subgroups. In IMP-po sitive patients, ATP/ADP and phosphocreatine/creatine ratios were sign ificantly lower than in IMP-negative patients. IMP-positive patients w ere furthermore characterized by a significantly lower DLCO. The resul ts of this study indicate an imbalance between the utilization and res ynthesis of ATP in resting muscle of patients with stable COPD.