Increased capillaries in mitochondrial myopathy: Implications for the regulation of oxygen delivery

Tanja Taivassalo, Karen Ayyad, Ronald G. Haller

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Human skeletal muscle respiratory chain defects restrict the ability of working muscle to extract oxygen from blood, and result in a hyperkinetic circulation during exercise in which oxygen delivery is excessive relative to oxygen uptake and oxygen levels within contracting muscle are abnormally high. To investigate the role of the muscle microcirculation in this anomalous circulatory response and possible implications for the regulation of muscle angiogenesis, we assessed muscle oxidative capacity during cycle exercise and determined capillary levels and distribution and vascular endothelial growth factor expression in quadriceps muscle biopsies in patients with mitochondrial myopathy attributable to heteroplasmic mitochondrial DNA mutations. We found that in patients with mitochondrial myopathy, muscle capillary levels were twice that of sedentary healthy subjects (3.0±0.9 compared with 1.4±0.3, P<0.001) despite the fact that oxygen utilization during peak cycle exercise was half that of control subjects (11.1±4.0ml/kg/min compared with 20.7±7.9ml/kg/min, P<0.01); that capillary area was greatest in patients with the most severe muscle oxidative defects and was more than two times higher around muscle fibre segments with defective (i.e. cytochrome oxidase negative/succinic dehydrogenase-positive or 'ragged-red' fibres) compared with more preserved respiratory chain function; and that vascular endothelial growth factor expression paralleled capillary distribution. The increased muscle capillary levels in patients correlated directly (r 2=0.68, P<0.05) with the severity of the mismatch between systemic oxygen delivery (cardiac output) and oxygen utilization during cycle exercise. Our results suggest that capillary growth is increased as a result of impaired muscle oxidative phosphorylation in mitochondrial myopathy, thus promoting increased blood flow to respiration-incompetent muscle fibres and a mismatch between oxygen delivery and utilization during exercise. Furthermore, the finding of high capillary levels despite elevated tissue oxygen levels during exercise in respiration-deficient muscle fibres implies that mitochondrial metabolism activates angiogenesis in skeletal muscle by a mechanism that is independent of hypoxia.

Original languageEnglish (US)
Pages (from-to)53-61
Number of pages9
JournalBrain
Volume135
Issue number1
DOIs
StatePublished - Jan 2012

Fingerprint

Mitochondrial Myopathies
Oxygen
Muscles
Exercise
Electron Transport
Vascular Endothelial Growth Factor A
Capillary
Respiration
Skeletal Muscle
Succinate Dehydrogenase
Oxidative Phosphorylation
Quadriceps Muscle
Electron Transport Complex IV
Microcirculation
Mitochondrial DNA
Cardiac Output

Keywords

  • angiogenesis
  • mitochondrial DNA defects
  • oxidative metabolism
  • regulation of oxygen delivery
  • skeletal muscle

ASJC Scopus subject areas

  • Clinical Neurology
  • Arts and Humanities (miscellaneous)

Cite this

Increased capillaries in mitochondrial myopathy : Implications for the regulation of oxygen delivery. / Taivassalo, Tanja; Ayyad, Karen; Haller, Ronald G.

In: Brain, Vol. 135, No. 1, 01.2012, p. 53-61.

Research output: Contribution to journalArticle

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