Aging
Conditions
Keywords
Passive heating, Aging, Microvascular, Autophagy
Brief summary
Vascular dysfunction is a common factor in many chronic debilitating diseases, contributing to morbidity and mortality. With the onset of chronic disease or exposure to stress, the vasculature displays an inability to adequately respond to increased blood flow demands, manifesting in a reduced ability or altered mechanism of vasodilation. Aging is an independent risk factor in the development of cardiovascular disease, and reduces vasodilator capacity, or alters the mechanism by which vasodilation occurs in multiple vascular beds. Chronic exercise/physical activity is one of the most potent ways to enhance vascular function, resulting in favorable outcomes such as reductions in blood pressure, and improved ability to perform activities of daily living. Barriers to exercise or failure of long-term adherence preclude many populations from the cardiovascular benefits of exercise, thus further enhancing cardiovascular risk. Avenues to mimic blood flow patterns observed with exercise may exert beneficial effects without the need for the ability to exercise. Recent evidence has demonstrated that passive heat therapy, or chronic heat exposure (\ +1°C in core temperature) results in reductions in major adverse cardiovascular events, blood pressure and improved large artery endothelial function, primarily through preservation of large artery function in response to vascular stress. It is unclear whether microvascular function is augmented in response to acute heat exposure, or whether this can protect against vascular insults particularly in older adults. Some preliminary evidence in humans suggest that autophagy, a cell recycling process is involved in the beneficial cardiovascular effects, as short-term heat exposure upregulates markers of autophagy. Previous evidence from our lab indicates that autophagy governs the mechanism by which microvascular vasodilation occurs. The role of autophagy in mediating the beneficial effects of passive heating is unknown.
Interventions
PROCEDUREPassive Heating
The lower limbs will be immersed in warm (42C) circulating water for 60 minutes.
DRUGL-NAME
L-NAME will be used during measurement of cutaneous microvascular function to test the dependency upon NO to elicit vasodilation.
Sponsors
William Hughes
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
* Participants must be between 18-80 yrs. of age * No more than 1 cardiovascular risk factor (see list in
Exclusion criteria
)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in cutaneous microvascular function | Baseline, 60 minutes post I/R, and 60 minutes post hot water immersion + I/R injury | Change in cutaneous microvascular function assessed via microdialysis infusion of acetylcholine (dose response) in the presence and absence of L-NAME to test the dependency upon NO to elicit vasodilation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Spontaneous baroreflex sensitivity | Baseline, 60 minutes post I/R, 60 minutes post hot water immersion + I/R injury | Change in spontaneous BRS |
| 24-hour (Ambulatory) Blood Pressure | Baseline | Ambulatory blood pressure (systolic, diastolic) for both peripheral and aortic blood pressure |
| Change in plasma concentration of heat shock proteins | Baseline and 60 minutes post hot water immersion | Change in the plasma concentrations of various heat shock proteins (HSP 70, 90) |
Countries
United States
Contacts
Primary ContactWilliam E Hughes, Ph.D.
Outcome results
None listed