Endothelial Dysfunction
Conditions
Keywords
heat therapy, exercise training, endothelial function
Brief summary
This study will explore the effects of 8 weeks of local leg heat therapy, exercise training, or both on measures of vascular function, cardiorespiratory fitness, and muscle strength in young, healthy individuals. Participants will be allocated into either a control group that will maintain their regular physical activity habits; or into one of three training groups: heat therapy will involve lower limb warm water immersion, exercise training will involve moderate-intensity cycling, and combined training will involve both performed in sequential order.
Detailed description
A between-groups interventional design will be used in a cohort of 80 young, healthy males and females 18-35 years old. Interested individuals will be invited to the lab for a screening and familiarization visit (1 hr), in which participants will be introduced to various lab testing protocols to ensure proper performance and tolerance during experimental data collection sessions. Participants will be randomized into one of four groups for an 8-week intervention period: (1) no training (CON), (2) lower limb heat therapy (HEAT), (3) moderate intensity cycling training (EX), or (4) combined training (HEATEX). CON will involve maintenance of regular physical activity habits. HEAT will involve 45 minutes of lower limb hot water immersion (42 °C) using a custom-made heating apparatus 3x/week. EX will involve of 45 minutes of cycling on an ergometer at 40-59% VO2reserve 3x/week. HEATEX will require participants to perform 3x/week of exercise training and heat therapy consecutively and in that order, such that each session is 90 minutes in duration. In total, all groups except CON will be expected to complete 24 intervention sessions. Vascular function will be characterized by measures of endothelial function, arterial stiffness, arterial structure, central hemodynamics, arterial blood flow and shear, and endothelial cell nitric oxide production. Muscle and metabolic adaptations will be characterized by measures of cardiorespiratory fitness, body composition, muscle strength and thickness, and fasting glucose and insulin. Inflammatory profile will be characterized by concentrations of interleukins, heat shock proteins, and cortisol. Thermal physiological adaptations will be characterized by measures of core and skin temperature and sweat rate. Perceptual responses will be characterized by measures of thermal comfort and sensation, calmness, alertness, mood, affect, and ratings of perceived exertion. Intervention adherence will be tracked throughout the intervention period. For the acute investigation (3-hr visit), outcome measures will be assessed before and immediately following the first and last training session. For the chronic investigation (2-hr visit), outcome measures will be assessed at weeks 0, 2, 4, 6, and 8 of the intervention period.
Interventions
OTHERHeat therapy
Lower limb warm water immersion (42 degrees C)
OTHERExercise training
Moderate-intensity cycling exercise (\ 40-59% VO2 reserve)
Sponsors
McMaster University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 35 Years
Healthy volunteers
Yes
Inclusion criteria
* Apparently healthy (i.e., no cardiovascular, musculoskeletal, or metabolic disease) * 18-35 years old * Recreationally and/or physically active
Exclusion criteria
* History of cardiovascular, musculoskeletal, or metabolic disease * Regular smoking and/or vasoactive drug use
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Brachial artery endothelial function | Change in endothelial function from week 0 to 8 | Flow-mediated dilation (FMD) is a measure of the ability of the artery to dilate in response to elevated shear stress, and represents endothelial function. For this technique, a pressure cuff will be wrapped around the forearm and then inflated to \ 200 mmHg for 5 minutes to occlude blood flow through the artery site. Doppler ultrasound (Vivid q, GE Medical Systems, Horten, Norway) and a 12 MHz linear array probe will be used to measure artery diameter before cuff inflation (rest), before cuff deflation (ischemia), and for three minutes after cuff deflation (reactive hyperemia). Images of the BA will be collected in Duplex mode and obtained proximal to the antecubital fossa. FMD will be calculated using this formula: FMD% = ((peak diameter-baseline diameter)/baseline diameter) × 100%. |
| Arterial stiffness | Change in arterial stiffness from week 0 to 8 | Pulse wave velocity (PWV) is a measure of the speed at which a pulse travels between two superficial artery sites, and represents arterial stiffness. For this outcome, applanation tonometers (i.e., micromanometer-tipped probes) (SPT-301, Millar Instruments, Houston, Texas, USA) will be used to detect and transmit pulse pressure wave forms at the carotid, femoral, and dorsalis pedis or tibialis posterior arteries. PWV will be calculated between the carotid-femoral arteries and femoral-foot arteries to quantify central and peripheral arterial stiffness, respectively, using this general formula: PWV = distance/pulse transit time. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Muscle strength | Change in muscle strength from week 0 to 8 | Knee extensor muscle strength will be assessed with an isokinetic dynamometer (Biodex). Participants will be familiarized with the testing procedures before assessment. Participants will be seated with restraining straps secured over the trunk, pelvis, and thigh; arms will be crossed over their chest. The axis of the dynamometer will be aligned with the axis of rotation of the knee joint. Participants will be asked to kick out repeatedly against the arm of the machine, and the force produced will be recorded. |
| Metabolic blood markers | Change in metabolic markers from week 0 to 8 | Fasting insulin and glucose will be measured in blood plasma and serum. |
| Cardiorespiratory fitness | Change in cardiorespiratory fitness from week 0 to 8 | VO2peak represents the maximum rate of oxygen consumption that the body can attain, and is reliant on both oxygen delivery to muscles and oxygen utilization by muscles. In this VO2peak test, participants will cycle on a cycle ergometer (Excalibur Lode B.V., Groningen, The Netherlands) at an intensity that begins at 50 W and progressively increases at a rate of 1 W every 2 seconds until volitional exhaustion or a pedaling cadence \< 60 rpm. A mask equipped with a breath-by-breath gas analyzer (Quark CPET, COSMED, Rome, Italy) will be worn to obtain the ratio of CO2 produced to O2 consumed, and a HR monitor (Polar Electro Oy, Kempele, Finland) will be worn to monitor HR throughout the duration of the test. VO2peak will be calculated using this formula: VO2peak = (VI \* FIO2) - (VE \* FEO2). |
| Endothelial cell nitric oxide production markers | Change in endothelial nitric oxide production from week 0 to 8 | Endothelial nitric oxide synthase protein content and activity, and nitric oxide and superoxide anion production will be measured in human umbilical vein endothelial cell cultures bathed in serum collected from the study. |
| Heat shock protein mRNA and content | Change in heat shock proteins from week 0 to 8 | HSP72 and HSP90 will be measured in blood plasma and serum. |
| Core temperature | Change in core temperature from week 0 to 8 | Core temperature will be measured using a wireless telemetric pill during the acute experimental testing visits, and tympanic and rectal thermometry during all experimental testing visits. Participants will be instructed to swallow the pill with water 2-3 hours prior to each testing session. |
| Body composition | Change in body composition from week 0 to 8 | Body composition tests measure the proportions of fat mass and fat-free mass in the body. Participants will have their body composition assessed through air displacement plethysmography (BodPod). This method is non-invasive and involves \ 5 minutes of sitting still and quietly as the measurement is completed. |
Countries
Canada
Outcome results
None listed