       Document 0808
 DOCN  M95A0808
 TI    Metabolic abnormalities in skeletal muscle of patients receiving
       zidovudine therapy observed by 31P in vivo magnetic resonance
       spectroscopy.
 DT    9510
 AU    Sinnwell TM; Sivakumar K; Soueidan S; Jay C; Frank JA; McLaughlin AC;
       Dalakas MC; National Institute of Neurological Diseases and Stroke,
       National; Institutes of Health, Bethesda, Maryland 20892, USA.
 SO    J Clin Invest. 1995 Jul;96(1):126-31. Unique Identifier : AIDSLINE
       MED/95340811
 AB    Patients on long-term zidovudine (AZT) therapy experience muscle fatigue
       and weakness attributed to AZT-induced mitochondrial toxicity in
       skeletal muscle. To determine if the clinico-pathological abnormalities
       in these patients correspond to abnormal muscle energy metabolism, we
       used 31P in vivo magnetic resonance spectroscopy to follow
       phosphorylated metabolites during exercise. We studied 19 normal
       volunteers, 6 HIV-positive patients never treated with AZT, and 9
       HIV-positive patients who had been treated with AZT for a mean period of
       33 mo (range 12-48 mo) and had muscle biopsy-proven AZT-myopathy with
       abnormal mitochondria. Changes in phosphocreatine, ATP, and
       intracellular pH in the gastrocnemius muscle were followed during a
       graded steady state exercise protocol, and the recovery of
       phosphocreatine was followed on cessation of exercise. We found that
       graded steady state exercise produced a greater depletion of muscle
       phosphocreatine levels in the AZT-treated patients, compared to either
       HIV-positive patients who were not treated with AZT or normal controls.
       No differences in the effects of steady state exercise on muscle
       phosphocreatine levels were observed between the control group and the
       HIV-positive patients who had not been treated with AZT. The results
       suggest that the effect of AZT on muscle energy metabolism is
       significant, and similar to the effect observed in patients with known
       mitochondrial myopathies. Using a well-known model for control of
       mitochondrial metabolism, the observed differences in steady state
       phosphocreatine levels during exercise suggest that AZT treatment
       decreases the maximal work output and the maximal rate of muscle ATP
       synthesis.
 DE    Adenosine Triphosphate/ANALYSIS  Human  Hydrogen-Ion Concentration  HIV
       Infections/DRUG THERAPY/METABOLISM  Male  Muscle, Skeletal/*DRUG
       EFFECTS/METABOLISM  Nuclear Magnetic Resonance  Phosphocreatine/ANALYSIS
       Zidovudine/*ADVERSE EFFECTS  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

