Regeneration of Mitochondrial Function in Gastrocnemius Muscle in Peripheral Arterial Disease After Successful Revascularisation

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 (252.4-391.8) nmol/min/mg protein vs. CSA post-operative 438.5 (361.4-471.3) nmol/min/mg protein; p = .01) with post-operative return of values to the range of control subjects (CSA control 396.6 (308.2-435.9)). 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 (0.196-0.266) pmol/(secxmg) per CSA vs. post-operative 0.132 (0.116-0.150) pmol/(secxmg) per CSA, p = .007; E pre-operative 0.230 (0.195-0.279) pmol/(secxmg) per CSA vs. post-operative 0.129 (0.120-0.154) pmol/(secxmg) per CSA, p = .005) meaning a post-operative return of values to within the range of control subjects (P control 0.124 (0.080-0.155) pmol/(secxmg) per CSA; E control 0.121 (0.079-0.125) pmol/(secxmg) per CSA). Conclusion: With these results, it has been shown that the initially impaired mitochondrial function and content can normalise after revascularisation.