Effects of Passive Heat Therapy on Oxygen Consumption and Cardiovascular Fitness in Adults

The purpose of this study is to determine if enhanced endothelial arterial distensibility observed with heat therapy translates into improved cardiorespiratory fitness. The following aims are proposed: Aim 1: to determine if chronic heat therapy results in improvements in cardiovascular function. Aim 2: To examine potential mechanism(s) of action of heat therapy in cardiovascular function.

The National Institute of Health recognizes heart failure as a major public health problem with a prevalence of over 5.8 million Americans and 23 million people worldwide. Commonly prescribed medications to treat the symptoms associated with this disease are expensive and many are not covered by major health insurance companies. There is a critical need to develop novel treatment and prevention strategies for heart failure. Emerging research highlights the benefits of heat therapy (HT) on metabolic and cardiovascular disease risk. The Geiger laboratory has demonstrated that in obese rats fed a high- fat diet for 12 weeks, weekly HT restored whole body glucose tolerance and skeletal muscle insulin sensitivity. The first comprehensive investigation of long-term HT in young, sedentary humans resulted in improved endothelial function and hemodynamics that were on par with what is typically observed with exercise training in previously sedentary subjects. The purpose of this pilot study is to determine if the enhanced endothelial arterial distensibility observed with HT translates into improved cardiorespiratory fitness. The following aims are proposed: Aim 1: To determine if chronic HT results in improvements in cardiovascular function. The study team hypothesizes that repeated HT will result in improvement in hemodynamic variables related to arterial distensibility (blood pressure, stroke volume, stroke volume variation, cardiac index and systemic vascular resistance) and that these changes translate to improved cardiovascular function as measured by VO2max. Aim 2: To examine potential mechanism(s) of action of HT in cardiovascular function. The study team hypothesizes that HT may exerts its beneficial effects via the effect of heat shock proteins (HSPs) on Nitric Oxide (NO) bioavailability. This will be tested by measuring HSPs, NO mediators and inflammatory markers at baseline and post-intervention. There is rapidly growing interest in the use of HT as a global therapeutic approach and alternative or complementary therapy to exercise training for patients with chronic disease. Study findings would be clinically significant as both men and women with higher cardiorespiratory fitness (as indicated by maximal oxygen consumption, VO2max) are at lower risk for cardiovascular disease. These studies will be the first to examine the ability of chronic heat therapy to increase cardiorespiratory fitness as measured by maximal oxygen consumption, VO2max. These findings could lead to HT as a simple and effective tool for improving cardiovascular health in a variety of populations, particularly those with exercise limitations and comorbid disease states like type 2 diabetes, dementia and cardiovascular disease.

This study will recruit subjects to participate in heat therapy treatment at the University of Kansas Medical Center (KUMC). After pre-screening, informed consent, and enrollment, all subjects will have baseline hemodynamic assessments as well as VO2max measurements. Subjects will complete 10 heat therapy treatments over the course of 14 days. Hemodynamics will be assessed with the use of the Clearsight© fingertip blood pressure cuff. Within 24-48 hours after the last heat therapy experience, hemodynamic assessments and VO2max will be performed. Blood samples will be collected pre- and post intervention and analyzed for levels of nitric oxide mediators, heat shock protein levels and pro-anti-inflammatory markers.

Subjects will undergo 10 hot water immersions of 40.5 degrees Celsius for approximately 45 minutes per session over 14 days. Subjects will be immersed up to the shoulder until rectal temperature reacher 38.5 degrees Celsius (approximately 15-20 minutes). Subjects will then remain in the water bath submerged at waist level to maintain between 38.5 to 39.0 degrees Celsius for another 30 minutes. Following hot water immersion, subjects will be monitored for 10 minutes, or until temperature falls below 38.5 degrees Celsius.

Systolic and diastolic blood pressure will be monitored using the noninvasive Clearsight (Edward Lifesciences, Irvine, CA) monitor, which incorporates a disposable, single use fingertip cuff.

Blood pressure will be assessed at baseline and 24-48 hours after the last heat therapy session (end of study, ~2.5 weeks after first study visit). As a safety measure only, blood pressure will be monitored during every heat therapy treatment.

Stroke volume will be monitored using the noninvasive Clearsight (Edward Lifesciences, Irvine, CA) monitor incorporates a disposable, single use fingertip cuff.

Stroke volume will be assessed at baseline and 24-48 hours after the last heat therapy session (end of study, ~2.5 weeks after first study visit).

Stroke volume variation will be monitored using the noninvasive Clearsight (Edward Lifesciences, Irvine, CA) monitor incorporates a disposable, single use fingertip cuff.

Stroke volume variation will be assessed at baseline and 24-48 hours after the last heat therapy session (end of study, ~2.5 weeks after first study visit).

Cardiac index will be monitored using the noninvasive Clearsight (Edward Lifesciences, Irvine, CA) monitor incorporates a disposable, single use fingertip cuff.

Cardiac index will be assessed at baseline and 24-48 hours after the last heat therapy session (end of study, ~2.5 weeks after first study visit).

Systemic vascular resistance will be monitored using the noninvasive Clearsight (Edward Lifesciences, Irvine, CA) monitor incorporates a disposable, single use fingertip cuff.

Systemic vascular resistance will be assessed at baseline and 24-48 hours after the last heat therapy session (end of study, ~2.5 weeks after first study visit).

Maximum oxygen consumption (VO2max) will be measured using the Bruce Ramp protocol. The Bruce Ramp protocol is a standardized treadmill exercise commonly used in clinical laboratories.

VO2max assessment will be performed at baseline and 24-48 hours after the last heat therapy session (end of study, ~2.5 weeks after first study visit).

Serum levels of heat shock proteins (HSP72, HSP25) and the primary heat shock protein transcription factor (HSF1) will be assessed for change post heat therapy treatment.

Blood analyses will be performed at baseline and 24-48 hours after the last heat therapy session (end of study, ~2.5 weeks after first study visit).

Nitric oxide (NO) bioavailability will be assessed for change post heat therapy treatment by measuring nitric oxide and endothelial nitric oxide synthase (eNOS).

Blood analyses will be performed at baseline and 24-48 hours after the last heat therapy session (end of study, ~2.5 weeks after first study visit).

Pro/anti-inflammatory markers (IL1ra, IL-10, IL-8, IFN, and CRP) will be assessed for change post heat therapy treatment.

Blood analyses will be performed at baseline and 24-48 hours after the last heat therapy session (end of study, ~2.5 weeks after first study visit).

Exclusion Criteria: Current major cardiovascular disease (i.e.: recent myocardial infarction (heart attack), stroke, angina pectoris, high grade coronary vasculopathy or atherosclerosis, severe valvular disease, cardiac dysrhythmia that requires treatment. Current treatment with steroids or immunosuppressive agents Cancer Serious liver disease End-stage renal disease Judgement by medical provider that heat therapy poses an undue burden or risk Women who are pregnant or plan to become pregnant