Effect of Local Heat Stress Via Leg Bath on Artery Function (HEAT)

Arteries are flexible in their structure and function and change in response to a variety of factors. Endothelial cells, are the skin type cells that form a layer inside arteries, and they are very important for arterial health. When they work properly, they produce substances that make the artery enlarge and support a healthy environment; but when they do not work properly, they produce substances that make the artery constrict and lead to a harmful environment. We can measure the function of these cells using an ultrasound machine and a quick test. The application of heat has been shown to change the structure and function of arteries, but we need to understand how these changes happen before we can effectively use heat as a therapy. Limb heating protocols (e.g., leg bath), in contrast with whole-body heating modes (e.g., sauna), are appealing as therapies because they generally cost less and are easier to use; but evidence is needed to demonstrate that they work before widespread use can be considered. Imagine soaking your legs in a bathtub filled with warm water becoming part of the options you have for staying healthy. Clearly, there is a lot of potential for heat to be used as a therapy, particularly for people who are unable to, or have difficulty participating in other health interventions that are known to improve arterial, but we need to do this type of research before we are able to recommend warm foot baths for therapeutic purposes.

Study Overview

• Status: Completed
• Conditions: Endothelial Dysfunction
• Intervention / Treatment: Other: Lower limb hot water immersion

Detailed Description

A within-subjects interventional design will be used in a cohort of 16 young, healthy males and females between the ages of 18-35 years old. Interested individuals will be invited to the lab for a screening and familiarization visit, in which the brachial artery (BA) and superficial femoral artery (SFA) will be scanned to vet for ultrasound image quality and BA and SFA flow-mediated dilation tests will be performed to ensure participant tolerance during collection visits. According to current FMD guidelines, all qualified participants will be instructed to refrain from vigorous physical activity > 24 hours, alcohol and caffeine > 8 hours, and food > 6 hours prior to each of the two experimental visits. Participants will also be asked to ingest a wireless telemetry pill 2 hours prior to each of the two experimental visits. Upon arrival, basic anthropometric measures will be collected and hematocrit will be measured in duplicate with a finger prick blood sample equivalent to two 70 µl capillary tubes. Experimental visits will begin with 10 minutes of supine rest, while the participant is instrumented with skin temperature probes on the foot, calf, thigh, chest, and arm for measurement of skin temperature; single-lead ECG (Powerlab model ML795, ADInstruments, Colorado Springs, CO, USA) and non-invasive finger cuff (Finometer MIDI, Finapres, The Netherlands) for continuous heart rate and blood pressure monitoring. Following rest, BA and SFA FMD tests will be conducted to assess baseline endothelial function. Afterwards, single-point laser Doppler flowmetry focused on the forearm will be used to track skin blood flow continuously throughout heating. The heating protocol will involve participants immersing their lower limbs either up to the ankles or the knees in a 42 °C water bath for 45 minutes, in separate conditions. The order by which participants undergo these interventions will be randomized. Five minutes after the conclusion of the intervention, BA and SFA FMD tests will be conducted to assess endothelial function in the acute phase. BA and SFA blood velocities, blood flow turbulence, endothelial shear rate, and oscillatory shear index will be assessed before and during each of the interventions; and arterial stiffness defined as carotid-femoral pulse wave velocity (PWV) and common carotid artery (CCA) distensibility will be assessed before and after each of the interventions as additional outcomes. Participants will provide written informed consent prior to beginning any portion of the study.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8S 4L8
      • McMaster University Vascular Dynamics Lab

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Apparently health (i.e., no cardiovascular, musculoskeletal, or metabolic disease), 18-35 years old 18-35 years old Recreationally active (exercising 2-3 times per week)

Exclusion Criteria:

History of cardiovascular, musculoskeletal, or metabolic disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental; Lower limb hot water immersion	Other: Lower limb hot water immersion; Participants will undergo two interventions in separate visits: lower limb hot water (42 deg C) immersion up to the (1) ankles or (2) knees.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Flow-mediated dilation	Collected using vascular ultrasound and analyzed using semi-automated edge tracking software	Up to 2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Endothelial shear stress	Calculated using blood velocity and arterial diameter obtained from vascular ultrasound, and blood density and viscosity calculated using hematocrit	Up to 2 weeks
Pulse wave velocity	Collected using applanation tonometry and analyzed using data acquisition software	Up to 2 weeks
Arterial distensibility	Collected using ultrasound imaging and applanation tonometry, and analyzed using semi-automated edge tracking software and data acqusition software	Up to 2 weeks

Collaborators and Investigators

• Sponsor: McMaster University

Publications and helpful links

General Publications

• Brunt VE, Howard MJ, Francisco MA, Ely BR, Minson CT. Passive heat therapy improves endothelial function, arterial stiffness and blood pressure in sedentary humans. J Physiol. 2016 Sep 15;594(18):5329-42. doi: 10.1113/JP272453. Epub 2016 Jun 30.
• Gimbrone MA Jr, Garcia-Cardena G. Endothelial Cell Dysfunction and the Pathobiology of Atherosclerosis. Circ Res. 2016 Feb 19;118(4):620-36. doi: 10.1161/CIRCRESAHA.115.306301.
• Deanfield JE, Halcox JP, Rabelink TJ. Endothelial function and dysfunction: testing and clinical relevance. Circulation. 2007 Mar 13;115(10):1285-95. doi: 10.1161/CIRCULATIONAHA.106.652859. No abstract available.
• Brunt VE, Eymann TM, Francisco MA, Howard MJ, Minson CT. Passive heat therapy improves cutaneous microvascular function in sedentary humans via improved nitric oxide-dependent dilation. J Appl Physiol (1985). 2016 Sep 1;121(3):716-23. doi: 10.1152/japplphysiol.00424.2016. Epub 2016 Jul 14.
• Carter HH, Spence AL, Atkinson CL, Pugh CJ, Naylor LH, Green DJ. Repeated core temperature elevation induces conduit artery adaptation in humans. Eur J Appl Physiol. 2014 Apr;114(4):859-65. doi: 10.1007/s00421-013-2817-2. Epub 2014 Jan 8.
• Kellogg DL Jr. In vivo mechanisms of cutaneous vasodilation and vasoconstriction in humans during thermoregulatory challenges. J Appl Physiol (1985). 2006 May;100(5):1709-18. doi: 10.1152/japplphysiol.01071.2005.
• Naylor LH, Carter H, FitzSimons MG, Cable NT, Thijssen DH, Green DJ. Repeated increases in blood flow, independent of exercise, enhance conduit artery vasodilator function in humans. Am J Physiol Heart Circ Physiol. 2011 Feb;300(2):H664-9. doi: 10.1152/ajpheart.00985.2010. Epub 2010 Dec 3.
• Tinken TM, Thijssen DH, Hopkins N, Black MA, Dawson EA, Minson CT, Newcomer SC, Laughlin MH, Cable NT, Green DJ. Impact of shear rate modulation on vascular function in humans. Hypertension. 2009 Aug;54(2):278-85. doi: 10.1161/HYPERTENSIONAHA.109.134361. Epub 2009 Jun 22.
• Wong BJ, Hollowed CG. Current concepts of active vasodilation in human skin. Temperature (Austin). 2016 Jun 21;4(1):41-59. doi: 10.1080/23328940.2016.1200203. eCollection 2017.

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2019
• Primary Completion (Actual): March 15, 2019
• Study Completion (Actual): March 15, 2019

Study Registration Dates

• First Submitted: August 2, 2018
• First Submitted That Met QC Criteria: August 2, 2018
• First Posted (Actual): August 7, 2018

Study Record Updates

• Last Update Posted (Actual): August 13, 2019
• Last Update Submitted That Met QC Criteria: August 12, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: endothelial function; arterial stiffness; hot water immersion; heat stress
• Additional Relevant MeSH Terms: Wounds and Injuries; Heat Stress Disorders
• Other Study ID Numbers: HEAT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No