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2,4-Dinitrophenol, muscle biopsy, and McArdle's disease

Department of Neurology (Dr. Heller), Northwestern University Medical School, Chicago, IL, and the Department of Neurology and Neurosurgery (Dr. Brooke, Mr. Kaiser, and Ms. Choski), Washington University Medical School, St. Louis, MO.

Exercise is simulated in muscle biopsy preparations by using low concentrations of 2,4-dinitrophenol (DNP), which do not produce contracture or anatomic damage. The validity of this simulation is supported by (1) the biochemical effects of simultaneous muscle contraction and DNP are not additive, suggesting that exercise and DNP stress the same pathways; (2) the effects of increasing concentrations of DNP and increasing levels of stimulation are similar with an early drop in phosphocreatine, increasing lactate and inosine monophosphate (IMP), and a late fall in ATP levels; and (3) DNP provocation in a patient with McArdle's disease demonstrated an absence of lactate and high levels of IMP correlating with clinical findings. DNP provocation may be a simple way of studying metabolic pathways in neuromuscular diseases.

Address correspondence and reprint requests to Dr. Brooke, Washington University School of Medicine, Department of Neurology, 660 South Euclid, Box 8111, St. Louis, MO 63110.

Supported by a grant from the Muscular Dystrophy Association.

Received December 8, 1986. Accepted for publication in final form March 4, 1987.

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