P4700Work during treadmill rehabilitation predicts clinical benefit and muscle mitochondrial improvements in intermittent claudication

Abstract Background Supervised exercise training is recommended for intermittent claudication in peripheral artery disease (PAD), but the relationship between work achieved during exercise and clinical outcomes is not well described. As in other training modalities, increased effort measured by cumulative work production is expected to be translate into to positive performance adaptations. In settings of constrained limb blood flow, this relationship is unknown. In addition, the impact of exercise on skeletal muscle oxygen use capacity changes is unknown. Near infrared spectroscopy (NIRS) offers a method of characterizing skeletal muscle mitochondrial adaptations before and after training programs. Methods We enrolled subjects (n=17, age 71±8.8 years, 20% female) with PAD and intermittent claudication (ankle brachial index [ABI]=0.76±0.21) in a 12-week supervised training program, randomized to traditional pain-based training strategy versus hypoxia-based training (using NIRS to direct training). Muscle work was calculated based on training performance. NIRS-based determination of mitochondrial capacity and microvascular flow were measured at baseline and after 12 weeks. Results Subjects trained for an average of 32.9±5.9 sessions walking at 54.4±13.4 m/min per session. Subjects achieved a mean of average workload of 4767±5112 kilogram force meter (kpm) per session and an aggregate of 148536±148020 kpm for the training program. Baseline pain-free walking time of 2.95±2.10 minutes increased by a mean of 3.74±2.47 minutes. Increase in walking time was proportional to the average work level achieved per session, with a correlating trend to the overall work level performed over 12 weeks (r=0.543, p=0.024). There was no increase in blood flow measured by ABI or limb microcirculation perfusion index over the training period. Skeletal muscle mitochondrial capacity increased over the training period and correlated with the overall work performed (r=0.573, p=0.016). Figure 1 Conclusions Treadmill exercise rehabilitation for intermittent claudication may be guided by total dose of exercise and NIRS-based indices of mitochondrial capacity rather than pain-levels achieved or changes in perfusion measures. Acknowledgement/Funding American Heart Association