A Randomised Controlled Trial of Supervised Exercise Regimens and their Impact on Walking Performance, Skeletal Muscle Mass and Calpain Activity in Patients with Intermittent Claudication

Objectives Supervised exercise training (SET) is recommended for patients with intermittent claudication (IC). The optimal exercise programme has not been identified, and the potential adverse effects of exercise on these patients warrant consideration. Calpain proteases have been linked with tissue atrophy following ischaemia-reperfusion injury. High calpain activity may therefore cause muscle wasting in claudicants undergoing SET, and skeletal muscle mass (SMM) is integral to healthy ageing. This study assesses the impact of (1) treadmill-based SET alone; and (2) treadmill-based SET combined with resistance training on pain-free walking distance (PFWD), SMM, and calpain activity. Methods Thirty-five patients with IC were randomised to 12 weeks of treadmill only SET (group A), or combined treadmill and lower-limb resistance SET (group B). PFWD via a 6-minute walking test, SMM via dual energy X-ray absorptiometry, and calpain activity via biopsies of gastrocnemius muscles were analysed. Results Intention-to-treat analyses revealed PFWD improved within group A (160 m to 204 m, p =.03), but not group B (181 m to 188 m, p =.82). There was no between group difference (p =.42). Calpain activity increased within group A (1.62 × 10⁵ fluorescent units [FU] to 2.21 × 10 ⁵ FU, p =.05), but not group B. There was no between group difference (p =.09). SMM decreased within group A (-250 g, p =.11) and increased in group B (210 g, p =.38) (p =.10 between groups). Similar trends were evident for per protocol analyses, but, additionally, change in SMM was significantly different between groups (p =.04). Conclusions Neither exercise regimen was superior in terms of walking performance. Further work is required to investigate the impact of the calpain system on SMM in claudicants undertaking SET.