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

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.

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.

Eligibility Criteria:
Inclusion Criteria:

All subjects

* Capable of giving informed consent
* Any race or ethnicity
* Men and women age 21- 85 years (inclusive)
* Fluent in written and spoken English

Patients with peripheral arterial disease (PAD)

* Diagnosed with PAD (i.e., ankle-brachial index below 0.9)
* Fontaine stage II or less - no pain while resting
* Satisfactory history and physical exam

Healthy subjects

* Satisfactory history and physical examination
* Free of acute medical conditions

Exclusion Criteria:

For patients with PAD and Healthy subjects

* Age \< 21 years
* Pregnant or nursing women
* Decisional impairment
* Prisoners

For patients with PAD

* History of CAD with symptoms of unstable angina or myocardial infarction (\<6 months)
* History of epilepsy or seizure disorders

For healthy subjects

• Any other chronic diseases (heart, lung, neuromuscular disease or diabetes)