WHAT THIS PAPER ADDS Affected muscle regions in peripheral arterial disease (PAD) are known to be altered by reduced blood supply. Clinical research projects predominantly deal with the investigation of the underlying atherosclerotic lesions and the development of new technical devices for the treatment of those lesions. The investigation of the lower extremity PAD end organ, namely the muscle, has been neglected so far, and in particular the effect of revascularisation on affected muscle regions has not been evaluated. With this study it could be demonstrated that mitochondrial function in affected muscle regions is able to regenerate after revascularisation. Based on these findings, future studies assessing the clinical correlation between maximum walking distance and mitochondrial respiration could give additional information about underlying pathophysiological mechanism of muscle affected by PAD.Objective: Myopathy, characterised by altered mitochondrial function, is a central part of the pathophysiology of peripheral arterial disease and the aim of this study was to investigate the effect of revascularisation on mitochondrial function. Methods: High resolution respirometry was used to investigate mitochondrial respiration and the results were normalised to citrate synthase activity (CSA), a marker of mitochondrial content. Ten patients with symptomatic peripheral arterial disease (study group) and 10 subjects without ischaemia (control group) were included. Ankle brachial index and ultrasound imaging were performed before and after vascular intervention to confirm technically successful revascularisation. Within the study group, muscle biopsies from the gastrocnemius muscle were taken before vascular intervention and six weeks after revascularisation. Within the control group, tissue was harvested once. Results: There were no significant group differences regarding anthropometric data. CSA showed a significant increase after successful revascularisation (CSA pre-operative 281.4 (252.4e391.8) nmol/min/mg protein vs. CSA post-operative 438.5 (361.4e471.3) nmol/min/mg protein; p ¼ .01) with post-operative return of values to the range of control subjects (CSA control 396.6 (308.2e435.9)). Mitochondrial respiration normalised to CSA in oxidative phosphorylation (P) as well as in electron transfer (E) capacity were significantly reduced post-operatively when compared with pre-operative values (P pre-operative 0.218 (0.196e0.266) pmol/(secÂmg) per CSA vs. post-operative 0.132 (0.116e0.150) pmol/(secÂmg) per CSA, p ¼ .007; E pre-operative 0.230 (0.195e0.279) pmol/(secÂmg) per CSA vs. post-operative 0.129 (0.120e0.154) pmol/(secÂmg) per CSA, p ¼ .005) meaning a post-operative return of values to within the range of control subjects (P control 0.124 (0.080e0.155) pmol/(secÂmg) per CSA; E control 0.121 (0.079e0.125) pmol/(secÂmg) per CSA).Conclusion: With these results, it has been shown that the initially impaired mitochondrial function and content can normalise after revascularisation.

Background Peripheral arterial disease (PAD) is accompanied by myopathy characterized by mitochondrial dysfunction. The aim of this experimental study was to investigate the effect of revascularization procedures on mitochondrial function in ischemic and non-ischemic muscle. Methods Muscle biopsies from patients with symptomatic stage IIB/III PAD caused by isolated pathologies of the superficial femoral artery were obtained from muscle regions within the chronic ischemic muscle (gastrocnemius) and from non-ischemic muscle (vastus lateralis) before and 6 weeks after invasive revascularization. High-resolution respirometry was used to investigate mitochondrial function and results were normalized to citrate synthase activity (CSA). Results are given in absolute values and fold over basal (FOB). Results Respiratory states (OXPHOS (P) and electron transfer (E) capacity) normalized to CSA decreased while CSA was increased in chronic ischemic muscle after revascularization. There were no changes in in non-ischemic muscle. The FOB of chronic ischemic muscle was significantly higher for CSA (chronic ischemic 1.37 (IQR 1.10–1.64) vs. non-ischemic 0.93 (IQR 0.69–1.16) p = 0.020) and significantly lower for respiratory states normalized to CSA when compared to the non-ischemic muscle (P per CSA chronic ischemic 0.64 (IQR 0.46–0.82) vs non-ischemic 1.16 (IQR 0.77–1.54) p = 0.011; E per CSA chronic ischemic 0.61 (IQR 0.47–0.76) vs. non-ischemic 1.02 (IQR 0.64–1.40) p = 0.010). Conclusions Regeneration of mitochondrial content and function following revascularization procedures only occur in muscle regions affected by malperfusion. This indicates that the restoration of blood and oxygen supply are important mediators aiding mitochondrial recovery.