Peripheral artery disease (PAD), which affects 155 million people worldwide,1 is a debilitating condition characterized by functional impairment, exercise intolerance, and an increased risk of cardiovascular mortality.2 Patients with PAD face a sobering prognosis whereby pain and fatigue-related exercise intolerance cause a physically inactive lifestyle, which contributes to a further decline in functional capacity and quality of life.3,4 The role of exercise in staving off morbidity progression is well established,5,6 but adherence to exercise recommendations is attenuated outside the clinical setting for patients with PAD, because of exercise intolerance and a lack of external motivation.7,8 Thus, the amelioration of acute exercise tolerance is a goal that, if achieved, could have a positive impact on physical activity engagement in addition to immediate beneficial effects on exercise capacity. It is therefore important to explore simple, inexpensive, clinic- and home-based strategies that immediately improve exercise capacity in patients with PAD.
Lower leg heating (LLH) is one strategy easily deployed in both the clinic and home settings, which may acutely increase exercise capacity in patients with PAD. Acute limb heating (1) increases popliteal artery blood flow during9 and after10 heating, (2) increases perfusion of the distal microcirculation to both the skin and muscle,11 and (3) increases postheating vasoreactivity of the conduit arteries.12 Notably, blood flow changes with heating occur while limb oxygen consumption is unaffected.13 Recent research indicates that acute lower limb heating may induce beneficial cardiovascular effects in patients with PAD.10,14 However, to our knowledge, no investigation has examined the impact of lower limb heating on both leg perfusion and exercise capacity in this population. The aim of this pilot study therefore was to test the hypothesis that acute LLH (for 15 or 45 minutes) increases postheating popliteal artery blood flow and 6-minute walk distance (6MWD) in patients with PAD.
This pilot study was approved by the institutional review board of Salisbury University. Each subject gave his/her informed written consent before participation.
Six individuals (5 men and 1 woman) with PAD (claudication, Fontaine stage II), aged 69 ± 6.9 years (62–81 years), participated in this study. Inclusion criteria included a resting ankle-brachial index of less than 0.90, a body mass index of less than 35 kg/m2, and free of severe walking limitations due to comorbidity. For all study visits, subjects reported to the laboratory at least 3 hours postprandial, having refrained from alcohol consumption and exercise for 24 hours and consumption of caffeine for 12 hours. Subjects were instructed to take medications normally, as prescribed by their physicians. Please see the Table for subject characteristics.
Subjects reported to a temperature-controlled laboratory (21°C–22°C) for parallel experiments on three separate, randomized study visits, each separated by 2 to 7 days. Each study day, subjects were laid supine and instrumented with a 6-lead electrocardiogram (AD Instruments Dual Bio Amplifier/ECH 12-Lead Switch Box, Colorado Springs, Colorado). After 10 minutes of quiet rest, baseline measurements of single-leg popliteal artery blood flow (Doppler ultrasound; Philips Sonos 4500 ultrasound system, Amsterdam, the Netherlands) and arterial pressure (automated oscillometric device; Welch Allyn Vital Signs Monitor, Skaneateles Falls, New York) were taken in triplicate. Blood flow was measured on each subject's most affected leg, as indicated by the ankle-brachial index measurements furnished by his/her physician and confirmed by the subject's subjective report of signs and/or symptoms. For patients with no reported differences between legs, blood flow in the right leg was measured.
Mean blood velocities and diameters of the popliteal artery were measured using a linear ultrasound probe (Philips 11-3L Ultraband trapezoidal linear-array vascular transducer, Amsterdam, the Netherlands). The entire width of the artery was insonated with an angle of 60°, and velocity measurements were taken immediately before diameter measurements. A Doppler Audio Translator (Penn State Heart & Vascular Institute) was used to convert the 2 analog Doppler audio signals into a proportional time-varying flow velocity waveform that was recorded by the data acquisition system.15 Popliteal artery blood flow was calculated as artery cross-sectional area multiplied by popliteal mean blood velocity and reported as ml · min−1. Popliteal vascular conductance was calculated as popliteal artery blood flow/mean arterial pressure and expressed as ml · min−1 · mm Hg−1.
After baseline measurements, subjects were moved to a seated position to undergo bilateral LLH for either 15 or 45 minutes or 15 minutes of quiet rest (control visit). Quiet rest was used during the control visit because immersion of the leg in thermoneutral (room temperature) water would increase heat loss beyond that observed with thermoneutral air exposure, amounting to a mild cold exposure over the leg with resultant impacts on resting limb blood flow. The 45-minute duration of LLH was based on the current guidelines for supervised exercise therapy for patients with PAD.5 The 15-minute duration of LLH was included as a possible alternative to the 45-minute session, to which patients with PAD might be more compliant. Lower leg heating was carried out via water bath immersion at a depth of approximately 40 cm with the water temperature maintained at 42°C, via a water circulator/temperature controller device (VWR International, Radnor, Pennsylvania).
Immediately after LLH (or control), subjects returned to the supine position and measurements of popliteal artery blood flow and arterial pressure were taken in triplicate at 10, 20, and 30 minutes. After these measurements (35 minutes after intervention), subjects were instrumented with a wireless 6-lead electrocardiogram (Norav 1200W Stress ECG System, Wiesbaden, Germany) and performed a self-paced 6-minute walk test.16 Subjective ratings of perceived exertion, claudication, and dyspnea were collected each minute during the walk. In addition, subjects were asked to report their onset of claudication symptoms, if applicable.
The effect of heating condition (or control) on 6MWD and distance to the onset of claudication was assessed by a 1-way repeated-measures analysis of variance. The effects of heating condition (or control) and heat application (pre/post) on popliteal artery blood flow and vascular conductance were assessed by a 2-way repeated-measures analysis of variance. The Holm-Sidak post hoc test was used where appropriate; α was set to .05. All values are reported as mean ± SEM, unless otherwise noted.
Subject characteristics are presented in the Table. The effects of acute LLH for 15 and 45 minutes on resting popliteal artery blood flow (30 minutes postheating) and 6MWD are displayed in the Figure. There was a significant time (pre/post) × session interaction effect on popliteal artery blood flow (F = 11.059, P = .003). The 15-minute LLH session increased popliteal artery blood flow from 89.1 ± 11.9 to 172.6 ± 19.8 mL· min−1 (93.7%; P = .019), whereas the 45-minute LLH session increased popliteal artery blood flow from 78.9 ± 13.5 to 266.8 ± 57.8 mL · min−1 (238.2%; P = .002). The magnitude of popliteal artery blood flow postheating increased in a (heating) duration-dependent manner (P < .05 vs control for both heating conditions and between 15- vs 45-minute heating). Baseline popliteal artery blood flow was similar between conditions, and responses in popliteal vascular conductance mirrored the blood flow responses.
Lower leg heating increased 6MWD from 1021.7 ± 109.3 feet in the control session to 1126.0 ± 121.8 feet (10.2%; P = .018) in the 15-minute session and 1139.9 ± 131.0 feet (11.6%; P = .009) in the 45-minute session. Distance walked was not different between heating sessions. Rating of perceived exertion in the final minute of exercise was lower in the 45-minute session (13.0 ± 0.8) than the control and 15-minute sessions (14.0 ± 0.7 and 14.2 ± 0.5, respectively; both Ps < .05), whereas distance to the onset of claudication symptoms was not different between conditions (P = .18).
The goal of this pilot study was to determine the effect of acute LLH (for 15 or 45 minutes) on resting popliteal artery blood flow and 6MWD in patients with PAD. In support of our hypothesis, both 15- and 45-minute heating sessions increased postheating popliteal artery blood flow and 6MWD, evoking similar improvements in distance walked (≥10%). Furthermore, LLH reduced perceived exertion even while walking pace increased, albeit only in the 45-minute heating session. These results suggest that as little as 15 minutes of LLH, via water immersion, increases leg perfusion and improves acute walking capacity in these patients. Thus, LLH shows promise as a novel and practical intervention to acutely improve exercise capacity in patients with PAD.
There are some limitations to our preliminary investigation. First, this study was performed on a relatively small sample size; however, all subjects demonstrated increased popliteal artery blood flow and improved 6MWD with heating. Second, although we demonstrated that both popliteal artery blood flow and 6MWD increased after LLH, the degree to which these improvements in walking capacity can be attributed to increases in leg perfusion, per se, is unclear. It is possible that another stimulus associated with LLH, such as warming of the muscles, thus altering enzyme kinetics, may have contributed to the improved 6MWD in these patients. Along those lines, 6MWD after 45 minutes of LLH was only slightly farther than 6MWD after 15 minutes of LLH, despite substantially greater increases in popliteal artery blood flow after the 45-minute intervention. It is feasible that there is a blood flow threshold that must be met to adequately perfuse the working skeletal muscle in these patients and further increases in blood flow may hyperperfuse the muscle, thus delivering more oxygen and nutrients than are needed to support the metabolic demand of the exercise bout. Finally, although there is a trend for a delayed onset of reported claudication, this subjective measure was not statistically significant. Future studies may help to further elucidate the mechanisms underlying LLH as a tool to improve walking capacity in patients with PAD.
Perspectives and Clinical Significance
The current study is the first to demonstrate that acute LLH increases walking capacity in patients with PAD. Lower leg heating is a safe and inexpensive intervention that can be easily implemented in both clinic and home settings; therefore, it has the potential to improve exercise capacity in this population. If used regularly, LLH may be one of several interventions to improve exercise adherence in patients with PAD,17 thereby allowing the beneficial effects of exercise therapy to be observed and sustained with both home- and clinic-based exercise programs. These preliminary findings set the stage for future investigations examining the role of LLH as a therapy for patients with PAD.
What's New and Important
- As short as 15 minutes of LLH improves postheating popliteal artery blood flow and 6MWD in patients with claudication.
- Lower leg heating is an inexpensive intervention that can be easily implemented in both clinic and home settings.
- Lower leg heating shows promise as a strategy to improve exercise capacity in patients with PAD.
The authors thank the subjects who volunteered for this study. They also thank Dr Steven Hearne for his consultation and Christopher Evans, Joel Anderson, Rachel Prestridge, and Katherine Timmons for their technical assistance during this study.
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