Background: The mechanism of clinical improvement from supervised exercise training for claudication in peripheral arterial disease (PAD) is not well understood. Near infrared spectroscopy (NIRS) allows for real-time assessment of skeletal muscle blood flow. NIRS-derived post-exercise recovery of muscle oxygen consumption fit to a mono-exponential curve yields both a time constant (Tc) that is an index of mitochondrial capacity (i.e., oxygen use) as well as ability to measure reperfusion (T1/2 max, reflecting oxygen delivery).
Methods: To test the hypothesis that improvements in muscle oxygen use (training effects) rather than vascular oxygen delivery (microvascular effects) accounts for improvements in functional status after exercise training, we measured post-exercise NIRS-based assessment of mitochondrial capacity (Tc) and microcirculation (T1/2max) before and after a 12 week supervised exercise program in subjects with PAD. In addition, we tested whether ischemic calf pain versus calf-hypoxia measured by NIRS impacted training outcomes.
Results: Subjects with claudication from PAD trained thrice weekly for hour-long sessions over a 12 week period. Exercise intensity was determined by 15% reduction in resting skeletal muscle oxygenation by NIRS rather than by symptoms of pain. We randomly assigned subjects to NIRS-guided training (n=6, age 68.5±8.5, 33% female) versus traditional pain-based training (n=7, age 71.2±9.1 years, 29% female). Training cohorts were similar in baseline ankle-brachial index (ABI, 0.8±0.2 vs. 0.8±0.3, p=NS) and baseline symptom-free walking time on a Gardner graded treadmill test (3.5±1.8 vs. 1.7±0.9 min, p=NS). At the completion of 36 training sessions, NIRS-trained subjects demonstrated similar improvements in symptom-free walking time (mean 7.3±3.3 vs 6.3±3.5 min at 12 week follow up, p<0.01 for change from baseline and p=NS between cohorts) as the traditional pain-based cohort. In both NIRS-guided and pain-guided cohorts, measure of perfusion by ABI (p=0.3) and by T1/2 max for the entire cohort was unchanged (p=0.8). Meanwhile, mitochondrial oxidative capacity (Tc) improved in each PAD group (96.1±.0 to 50.0±8.8 sec, 75.2±43.0 to 59±21.0 sec, respectively; p<0.01 compared to baseline). T1/2 max was significantly higher in the PAD cohort compared with aged-matched controls without PAD (n=15; 94.0±52.2 vs. 17.9±8.3 sec, p<0.05).
Conclusions: Adaptations in mitochondrial oxidative capacity rather than improved tissue perfusion may account for improved walking times in subjects undergoing supervised exercise training in PAD.