The myopathy of peripheral arterial occlusive disease: Part 1. Functional and histomorphological changes and evidence for mitochondrial dysfunction

Iraklis I. Pipinos, Andrew R. Judge, Joshua T. Selsby, Zhen Zhu, Stanley A. Swanson, Aikaterini A. Nella, Stephen L. Dodd

Research output: Contribution to journalReview article

104 Scopus citations


In recent years, an increasing number of studies have demonstrated that a myopathy is present, contributes, and, to a certain extent, determines the pathogenesis of peripheral arterial occlusive disease (PAD). These works provide evidence that a state of repetitive cycles of exercise-induced ischemia followed by reperfusion at rest operates in PAD patients and mediates a large number of structural and metabolic changes in the muscle, resulting in reduced strength and function. The key players in this process appear to be defective mitochondria that, through multilevel failure in their roles as energy, oxygen radical species, and apoptosis regulators, produce and sustain a progressive decline in muscle performance. In this 2-part review, we highlight the currently available evidence that characterizes the nature and mechanisms responsible for this myopathy. In part 1, the authors review the functional and histomorphological characteristics of the myopathy and focus on the biochemistry and bioenergetics of its mitochondriopathy. In part 2, they then review accumulating evidence that oxidative stress related to ischemia reperfusion is probably the major operating mechanism of PAD myopathy. Important new findings of a possible neuropathy and a shift in muscle fiber type are also reviewed. Learning more about these mechanisms will enhance our understanding of the degree to which they are preventable and treatable.

Original languageEnglish (US)
Pages (from-to)481-489
Number of pages9
JournalVascular and Endovascular Surgery
Issue number6
StatePublished - Dec 1 2008



  • Bioenergetics
  • Mitochondrial dysfunction
  • Oxidative stress
  • Peripheral arterial occlusive disease
  • Skeletal muscle

ASJC Scopus subject areas

  • Surgery
  • Cardiology and Cardiovascular Medicine

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