Exercise testing as a diagnostic entity in mitochondrial myopathies

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Mitochondrion. 2004 Sep;4(5-6):529-42.

Exercise testing as a diagnostic entity in mitochondrial myopathies.

Tarnopolsky M.

Department of Pediatrics and Medicine (Neurology and Rehabilitation),

McMaster University, Hamilton, Canada.

Exercise intolerance is one of the most common symptoms in patients

with mitochondrial myopathies (MM). At the whole body level, this is

characterized by a reduction in maximal oxygen consumption (VO(2max))

with an excessive carbon dioxide production (VCO(2)), increased

rating of perceived exertion and a hyperdynamic circulatory response

at a given exercise intensity. Fewer patients with MM display overt

muscle atrophy and weakness even in the absence of a peripheral

neuropathy. At the level of the skeletal muscle, the abnormal

exercise response in MM patients is characterized by an increase in;

delivery of oxygen relative to extraction (reduced myoglobin or

hemoglobin desaturation), lactate production, phosphocreatine

hydrolysis and time of post-exercise PCr and ADP recovery.

Classically, the characterization of exercise intolerance is

performed using cycle ergometry with measurements of VO(2), VCO(2),

respiratory exchange ratio (RER=VCO(2)/VO(2)), heart rate, minute

ventilation, rating of perceived exertion, and cardiac output (where

available). Exercise protocols to maximum or for a given time period

at a set workload can differentiate MM from controls with a

sensitivity of 0.63-0.75 and a specificity of 0.70-0.90.

Modified hand-grip exercise protocols, especially if coupled with

simultaneous measurements of myoglobin/hemoglobin desaturation (near

infra-red spectroscopy) or venous oxygenation, can achieve similar or

higher levels of sensitivity and specificity. Similarly, exercise

coupled with muscle phosphocreatine/Pi ratios, PCr, pH or ADP

recovery kinetics, determined using magnetic resonance spectroscopy

are useful in differentiating MM, but are limited by availability,

experience and cost. In summary, aerobic exercise testing with some

measurement of oxygen consumption can be performed in most

institutions and can provide valuable information in the both the

work-up of patients with suspected MM as well as in the monitoring of

therapy in such patients.