Exercise intolerance, lactic acidosis, and abnormal cardiopulmonary regulation in exercise associated with adult skeletal muscle cytochrome c oxidase deficiency

R. G. Haller, S. F. Lewis, R. W. Estabrook, S. DiMauro, S. Servidei, D. W. Foster

Research output: Contribution to journalArticle

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Abstract

A 27-yr-old woman with lifelong severe exercise intolerance manifested by muscle fatigue, lactic acidosis, and prominent symptoms of dyspnea and tachycardia induced by trivial exercise was found to have a skeletal muscle respiratory chain defect characterized by low levels of reducible cytochromes a + a3 and b in muscle mitochondria and marked deficiency of cytochrome c oxidase (complex IV) as assessed biochemically and immunologically. Investigation of the pathophysiology of the exercise response in the patient revealed low maximal oxygen uptake (1/3 that of normal sedentary women) in cycle exercise and impaired muscle oxygen extraction as indicated by profoundly low maximal systemic arteriovenous oxygen difference (5.8 ml/dl; controls = 15.4 ± 1.4, mean ± SD). The increases in cardiac output and ventilation during exercise, normally closely coupled to muscle metabolic rate, were markedly exaggerated (more than two- to threefold normal) relative to oxygen uptake and carbon dioxide production accounting for prominent tachycardia and dyspnea at low workloads. Symptoms in our patient are similar to those reported in other human skeletal muscle respiratory chain defects involving complexes I and III, and the exaggerated circulatory response resembles that seen during experimental inhibition of the mitochondrial respiratory chain. These results suggest that impaired oxidative phosphorylation in working muscle disrupts the normal regulation of cardiac output and ventilation relative to muscle metabolic rate in exercise.

Original languageEnglish (US)
Pages (from-to)155-161
Number of pages7
JournalJournal of Clinical Investigation
Volume84
Issue number1
StatePublished - 1989

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Cytochrome-c Oxidase Deficiency
Lactic Acidosis
Skeletal Muscle
Exercise
Electron Transport
Oxygen
Muscles
Electron Transport Complex IV
Tachycardia
Cardiac Output
Dyspnea
Ventilation
Muscle Mitochondrion
Muscle Fatigue
Cytochromes b
Oxidative Phosphorylation
Workload
Carbon Dioxide

ASJC Scopus subject areas

  • Medicine(all)

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Exercise intolerance, lactic acidosis, and abnormal cardiopulmonary regulation in exercise associated with adult skeletal muscle cytochrome c oxidase deficiency. / Haller, R. G.; Lewis, S. F.; Estabrook, R. W.; DiMauro, S.; Servidei, S.; Foster, D. W.

In: Journal of Clinical Investigation, Vol. 84, No. 1, 1989, p. 155-161.

Research output: Contribution to journalArticle

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AU - Servidei, S.

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