NCT03900832

Effects of Heating on Exercise Pressor Reflex in Peripheral Artery Disease: Exercise Ability

• Status: Completed
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 33 (actual)
• Sponsor: Milton S. Hershey Medical Center · Academic / Other
• Sex: All
• Age: 21 Years – 85 Years
• Healthy volunteers: Accepted

Summary

The study objectives of this projects are to examine the hypothesis that the sympathetic and blood pressure responses to exercise will be attenuated during and after heat exposure in patients with peripheral artery disease, via altering the sensitivity of the muscle afferent receptors.

Detailed description

Peripheral arterial disease (PAD) affects 8-12 million Americans and its cardinal symptom is leg pain during exercise, termed "intermittent claudication". The diagnosis of PAD involves measuring the ankle-brachial index (ABI, i.e. the systolic pressure in the ankle divided by the systolic pressure in the arm); values below 0.9 are indicative of large vessel obstruction. Intermittent claudication is the most common symptom of this disease and it regularly occurs during exercise/physical activity but is relieved promptly by rest. Previous studies suggest that as the exercise pressor reflex is activated in patients with PAD, BP and heart rate (HR) are exaggerated. The BP rises during walking in the PAD patients were significantly greater than that seen in healthy control subjects. A recent human study from our group further indicates that an early BP response occurred during plantar flexion exercise before claudication was noted by the subjects, which may suggest that the accentuated BP response was due to an augmented muscle mechanoreflex in PAD. Moreover, another recent study from our group also showed that PAD patients have augmented renal vasoconstriction during plantar flexion exercise. It has been shown that exercise has benefits for patients with PAD. However, exercise becomes limited due to the pain and fatigue associated with the disease. Moreover, the augmented pressor response to exercise in PAD may increase the risk for the end organ damage (e.g. brain and/or heart). Thus, finding alternate/complimentary interventions that modulate the cardiovascular system and autonomic nervous system, and can be tolerated by the patients, would be beneficial. One possible intervention is heat exposure, since acute bouts of exercise and acute heat exposure have similar acute effects on both the autonomic and cardiovascular systems. For example, both exercise and heat exposure increase body temperature, increase HR, increase cardiac output (CO), increase left ventricular ejection fraction (EF), and enhance myocardial function. In the peripheral circulation, both exercise and heat exposure increase limb blood flow , muscle blood flow, and skin blood flow. Moreover, recent studies suggest that whole body exposure improves the endothelium function in PAD patients (e.g. activates endothelial progenitor cells CD34+). However, the effect of heat treatment on the ability of walking of PAD patients has not been examined. Moreover, it is unknown if heating can normalize/decrease the accentuated the pressor responses to exercise in PAD patients.

Conditions

• PAD

Interventions

Type	Name	Description
OTHER	Without Heating	Subject will complete walking protocol without any heating procedure
OTHER	Warm Bath	Subjects will sit in a warm bathtub with water up to their shoulders, while one arm will be out of water for BP and HR measurement. The water temperature and internal temperature (Tcore), BP and HR will be measured throughout the bath. The water temperature will be controlled between 38-41°C. Subjects will remain in the tub for ≤ 30 minutes. If the HR increases more than 15 -20 bpm, or a significant BP drop occurs (e.g. BP \>20 mmHg), the subject will be removed from the bath even if the time is \<30 min.
OTHER	Neutral Bath	Subjects will sit in a warm bathtub with water up to their shoulders, while one arm will be out of water for BP and HR measurement. The water temperature and internal temperature (Tcore), BP and HR will be measured throughout the bath. The water temperature will be controlled between 35 - 37°C. Subjects will remain in the tub for ≤ 30 minutes.
OTHER	Heating Suit	The mean skin temperature Tsk will be controlled with a water-perfused suit worn by subjects. Whole-body heating will be accomplished by perfusing warm water (\~ 45 - 50 °C) through the suit to elevate the Tsk to ≤ 38 °C (100 oF). Warm water is through plastic tubes, and subjects' skin will not directly touch warm water. The heating will be continued until the ∆Tcore reaches \~ 0. 6 - 1.0 °C. This may take approximately 60 - 90 min.
OTHER	Lower limb warm water immersion	Subjects will sit on a chair and put their lower legs and feet in a bucket with warm water. The water level will be just below the knees (depth of approximately 40 cm). The water temperature will be monitored and controlled at \~38 - 42 °C throughout the 30 minutes. BP, HR, Tcore, the skin temperature and skin blood flow (e.g. on a thigh and/or forearm) will be measured before, during and after the lower limbs warm water immersion.
OTHER	Gardner walking protocol	The Gardner protocol begins at 2 mph and 0% grade for 2 minutes. The grade increases by 2% every 2 minutes (the speed remains 2 mph) until the subject says they want to stop or 22 minutes maximum. BP and HR will also be measured throughout the protocol.

Timeline

• Start date: 2019-05-15
• Primary completion: 2025-07-31
• Completion: 2025-07-31
• First posted: 2019-04-03
• Last updated: 2025-09-16

Locations

1 site across 1 country: United States