Effects of exercise training on calf muscle oxygen extraction and blood flow in patients with peripheral artery disease

Abstract

We employed near-infrared optical techniques, diffuse correlation spectroscopy (DCS), and frequency-domain near-infrared spectroscopy (FD-NIRS) to test the hypothesis that supervised exercise training increases skeletal muscle microvascular blood flow and oxygen extraction in patients with peripheral artery disease (PAD) who experience claudication. PAD patients ( n = 64) were randomly assigned to exercise and control groups. Patients in the exercise group received 3 mo of supervised exercise training. Calf muscle blood flow and oxygen extraction were optically monitored before, during, and after performance of a graded treadmill protocol at baseline and at 3 mo in both groups. Additionally, measurements of the ankle-brachial index (ABI) and peak walking time (PWT) to maximal claudication were made during each patient visit. Supervised exercise training was found to increase the maximal calf muscle blood flow and oxygen extraction levels during treadmill exercise by 29% (13%, 50%) and 8% (1%, 12%), respectively [ P < 0.001; median (25th percentile, 75th percentile)]. These improvements across the exercise group population were significantly higher than corresponding changes in the control group ( P < 0.004). Exercise training also increased PWT by 49% (18%, 101%) ( P = 0.01). However, within statistical error, the ABI, resting calf muscle blood flow and oxygen extraction, and the recovery half-time for hemoglobin\myoglobin desaturation following cessation of maximal exercise were not altered by exercise training. The concurrent monitoring of both blood flow and oxygen extraction with the hybrid DCS/FD-NIRS instrument revealed enhanced muscle oxidative metabolism during physical activity from exercise training, which could be an underlying mechanism for the observed improvement in PWT. NEW & NOTEWORTHY We report on noninvasive optical measurements of skeletal muscle blood flow and oxygen extraction dynamics before/during/after treadmill exercise in peripheral artery disease patients who experience claudication. The measurements tracked the effects of a 3-mo supervised exercise training protocol and revealed that supervised exercise training improved patient ability to increase microvascular calf muscle blood flow and oxygen extraction during physical activity.

A low-cost, wireless near-infrared spectroscopy device detects the presence of lower extremity atherosclerosis as measured by computed tomographic angiography and characterizes walking impairment in peripheral artery disease

“…In our experience, this protocol can be completed within 15 minutes and could reasonably be performed at the time of a clinic visit. We anticipate that therapies that improve, leg hemodynamics, muscle perfusion, oxygen balance, and/or ischemic myopathy would show improvements in NIRS profiles as has been shown by Baker et al, 34 Beckitt et al, 35 and Henni et al 36 However, it is not likely that NIRS devices have the capacity to decipher the precise mechanisms (improved hemodynamics vs improved myopathy, etc) behind the documented enhancements of the StO 2 and additional testing of muscle perfusion, biochemistry and histology should be included to address this type of more complicated mechanistic questions.…”

“…However, these findings were not reflected in resting measurements of blood flow or resting muscle StO 2 . 34 Similarly, Beckitt et al 35 studied patients with PAD receiving exercise therapy or successful angioplasty and did not report changes in resting gastrocnemius StO 2 , but found significant decrease in calf muscle desaturation at a submaximal exercise time point of 100 seconds in both the exercise and angioplasty cohorts. Furthermore, in a limited study of a single patient treated by angioplasty of iliac stenosis, Henni et al 36 showed that transcutaneous oxygen measures obtained during exercise testing are normalized after revascularization.…”

“…This finding suggests StO 2 is an appropriate surrogate of local oxygen availability and, therefore, useful in understanding the changes in the calf muscle oxygenation during exercise. 33 Baker et al 34 have reported enhanced maximal calf muscle blood flow and oxygen extraction after 3 months of exercise therapy in patients with PAD, using a device that combined the capability of frequency domain NIRS with that of diffuse correlation spectroscopy. However, these findings were not reflected in resting measurements of blood flow or resting muscle StO 2 .…”

Studies into the determinants of skeletal muscle oxygen consumption: novel insight from near‐infrared diffuse correlation spectroscopy

“…Diffuse correlation spectroscopy (DCS) is emerging as a powerful new tool to assess skeletal muscle perfusion (Gurley et al 2012;Henry et al 2015;Baker et al 2017;Carp et al 2017;Shang et al 2017;Bangalore-Yogananda et al 2018;Hammer et al 2018). DCS is completely non-invasive, has excellent temporal resolution (Bi et al 2015) and has been validated in a variety of organs and tissues against several different standards, including laser Doppler (Shang et al 2011), xenon-CT (Kim et al 2014), fluorescent microsphere flow measurements (Zhou et al 2009) and arterial spin labelled-MRI (Yu et al 2007).…”

“…Combining DCS with conventional near-infrared spectroscopy (NIRS) -an established technique for characterizing the transport and utilization of oxygen through the microcirculation (Belardinelli et al 1995;DeLorey et al 2003DeLorey et al , 2004Grassi et al 2003;Ferreira et al 2005;Broxterman et al 2014Broxterman et al , 2015Koga et al 2014;Grassi & Quaresima, 2016;Sun et al 2016;Barstow, 2019)introduces exciting new possibilities for understanding the determinants of muscle oxygen utilization at the microvascular level. Several laboratories have already combined DCS with conventional NIRS during exercise, establishing good 'proof-of-concept' (Henry et al 2015;Baker et al 2017;Carp et al 2017;Hammer et al 2018); however, none of these prior investigations have directly compared NIRS-DCS to conventional Fick determinants of oxygen delivery (i.e. bulk skeletal muscle blood flow) and utilization (i.e.…”