Full research paper Near infrared spectroscopy-guided exercise training for claudication in peripheral arterial disease Jonathan R Murrow 1 , Jared T Brizendine 2 , Bill Djire 3 , Hi-Ju Young 2 , Stephen Rathbun 4 , Kent R Nilsson Jr 1 and Kevin K McCully 4 Abstract Rationale: Supervised treadmill exercise for claudication in peripheral arterial disease is effective but poorly tolerated because of ischemic leg pain. Near infrared spectroscopy allows non-invasive detection of muscle ischemia during exercise, allowing for characterization of tissue perfusion and oxygen utilization during training. Objective: We evaluated walking time, muscle blood flow, and muscle mitochondrial capacity in patients with peripheral artery disease after a traditional pain-based walking program and after a muscle oxygen-guided walking program. Method and results: Patients with peripheral artery disease trained thrice weekly in 40-minute-long sessions for 12 weeks, randomized to oxygen-guided training (n ¼ 8, age 72  9.7 years, 25% female) versus traditional pain-based training (n ¼ 10, age 71.6  8.8 years, 20% female). Oxygen-guided training intensity was determined by maintaining a 15% reduction in skeletal muscle oxygenation by near infrared spectroscopy rather than relying on symptoms of pain to determine exercise effort. Pain free and maximal walking times were measured with a 12-minute Gardner treadmill test. Gastrocnemius mitochondrial capacity and blood flow were measured using near infrared spectroscopy. Baseline pain- free walking time was similar on a Gardner treadmill test (2.5  0.9 vs. 3.6  1.0 min, p ¼ 0.5). After training, oxygen- guided cohorts improved similar to pain-guided cohorts (pain-free walking time 6.7  0.9 vs. 6.9  1.1 min, p < 0.01 for change from baseline and p ¼ 0.97 between cohorts). Mitochondrial capacity improved in both groups but more so in the pain-guided cohort than in the oxygen-guided cohort (38.8  8.3 vs. 14.0  9.3, p ¼ 0.018). Resting muscle blood flow did not improve significantly in either group with training. Conclusions: Oxygen-guided exercise training improves claudication comparable to pain-based training regimens. Adaptations in mitochondrial function rather than increases in limb perfusion may account for functional improvement. Increases in mitochondrial oxidative capacity may be proportional to the degree of tissue hypoxia during exercise. Keywords Peripheral arterial disease, claudication, near-infrared spectroscopy, mitochondria Received 29 March 2018; accepted 27 July 2018 Introduction Claudication disables millions of patients with lower extremity atherosclerotic peripheral artery disease (PAD). 1 Hemodynamic constraints to the supply of oxygen and substrates to skeletal muscle result in ische- mia when walking. The poor correlation between blood flow measures and symptoms, however, suggests that adverse adaptations such as skeletal muscle mitochon- drial dysfunction play a pathophysiologic role. 2–4 Supervised treadmill exercise training programs 1 Augusta University – University of Georgia Medical Partnership, USA 2 University of Alabama Birmingham, USA 3 Mercer University, Athens, Georgia, USA 4 University of Georgia, Athens, Georgia, USA Corresponding author: Jonathan R Murrow, University of Georgia Health Sciences Campus, Winnie Davis Hall 203, 108 Spear Road, Athens, GA 30602, USA. Email: jmurrow@uga.edu European Journal of Preventive Cardiology 0(00) 1–10 ! The European Society of Cardiology 2018 Article reuse guidelines: sagepub.com/journals-permissions DOI: 10.1177/2047487318795192 journals.sagepub.com/home/ejpc