Heat, Microvascular Function and Aging

William Hughes

Status and phase

Enrolling

Early Phase 1

Conditions

Aging

Treatments

Procedure: Passive Heating

Drug: L-NAME

Study type

Interventional

Funder types

Other

Identifiers

NCT06633198

PRO00052867

Details and patient eligibility

About

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.

Enrollment

20 estimated patients

Sex

All

Ages

18 to 80 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

Participants must be between 18-80 yrs. of age
No more than 1 cardiovascular risk factor (see list in exclusion criteria)

Exclusion criteria

Cardiovascular Risk Factors
Uncontrolled/unmanaged hypertension and/or use of current anti-hypertensive therapy
Current Tobacco product use or within last 6 months
BMI greater than 30
Hyperlipidemia - diagnosed and/or taking medications to manage
Hypercholesterolemia - diagnosed and/or taking medications to manage (e.g. statins)
Type 1 or Type 2 Diabetes
Use of anti-coagulant or anti-platelet drugs
Use of beta blockers
Symptomatic coronary artery disease
Diagnosed Heart Failure (Any classification above Class I as defined by NY Heart Association)
Diagnosed renal impairment Renal impairment defined, according to National Kidney Foundation as abnormalities of kidney structure or function, present for greater than 3 months, including:
Albuminuria (ACR ≥ 30 mg/g)
Urine sediment abnormalities
Electrolyte and other abnormalities due to tubular disorders
Structural abnormalities detected by imaging
History of kidney transplantation
Decreased glomerular filtration rate (GFP < 60 mL/min/1.73 m2)
Current Hormone Replacement Therapy Use
History of retinopathy
Documented neuromuscular disorders
Porphyria Cutanea Tarda (blistering of skin to sun; photosensitivity)
Pregnancy (Young Female subjects)
Allergies to povidone iodine
Tattoos on lower arm (forearm)
Use of erectile dysfunction medication in the past 6 months
Use of topical/non-topical steroids in last 6 months (e.g. cortisone cream)
Active anti-cancer treatment or treatment within last 12 months
Active COVID-19 or within the past 3 months
Gender Reassignment Therapy