A New Model for Cutaneous Thermal Hyperemia

Patricia Choi, Naoto Fuji and Vienna Brunt

Mentor: Christopher Minson

PM Poster Presentation

Poster 8

Currently, assessment of cutaneous thermal hyperemia is done by locally heating the skin from a baseline of 33 to 42C at a rate of 0.1oC/1 s. The purpose of this study was to characterize the hyperemic response using different rates of heating from the traditional protocol, specifically 0.1oC/1s, 0.1oC/10s, 0.1oC/60s, and three target temperatures, 36, 39, 42 oC. Six subjects (3 males and 3 females) within the age group of 22-25 participated in all six protocols. Skin sites were locally heated on the forearm from a baseline of 33oC to three target temperatures at each of the three rates. After an hour of maintaining the target temperature, the three sites were heated to 43.5 oC to attain maximal skin blood flow (SkBF). SkBF was measured with Laser Doppler flow metery. Data are presented as % maximal cutaneous vascular conductance (CVC),which equals blood flow divided by mean arterial pressure. The new protocol attenuated plateau CVC from 95.3 ± 3.22% of the standard protocol to 33.8 ± 2.69% with 36 C at 0.1C/1s (p< 0.01), 53.7 ± 1.3% with 39C at 0.1C/s (p < 0.01), 29.6 ± 1.5% with 36C at 0.1C/10s (p< 0.01), 45.9 ± 1.7% with 39C at 0.1C/10s (p< 0.01), 25.47 ± 1.3% with 36C at 0.1C/60s (p< 0.01). We suggest that heating at different rates and to target temperatures from the standard heating protocol exhibit different hyperemic profiles.

Impact of Estradiol and Progesterone on Muscle Sympathetic Nerve Activity in Young, Healthy Women

Presenters: Elisabeth Barrar, J.C. Miner, and J.A. Miner

Mentor: Christopher Minson

PM Poster Presentation

Poster 2

Alterations in muscular sympathetic nerve activity (MSNA) in healthy, young women (<40 years of age) have been seen during the early follicular phase of the menstrual cycle. Furthermore, oral contraceptives have also shown alterations in MSNA in active weeks versus placebo weeks. However, the independent effects of the hormones are unclear. PURPOSE: To investigate the independent effects of exogenous estradiol and progesterone on MSNA in young, healthy women. We hypothesized that administration of estradiol would increase MSNA burst incidence and burst frequency and that MSNA would not change with administration of progesterone in young, healthy women. METHODS: 18 young, healthy women subjects (BMI 18-25kg/m2) were studied under hormone suppression (with go- nadotropin-releasing hormone antagonist). Subjects were studied a second time following 2-3 days of either 0.2mg/day of transdermal estradiol supplementation (n=10) or 200mg/day of oral progesterone supplementation (n=8). On each study day, baseline MSNA in the peroneal nerve was recorded via microneurography for 10 minutes, and burst frequency and burst incidence were calculated. RESULTS: Estradiol decreased MSNA burst frequency from 8.39 to 5.40 bursts/min (p=0.02) and burst incidence from 14.51 to 9.18 bursts/100 heart beats (p=0.01). However, there were no significant differences following progesterone administration. CONCLUSIONS: Estradiol, but not progesterone, administration in young healthy women decreases resting baseline sympathetic activity.

Testing Different Models for Cutaneous Thermal Hyperemia

Presenter : Patricia Choi

Mentor : Christopher Minson

Major : Human Physiology

Poster 2

Currently, the assessment of cutaneous thermal hyperemia is done by locally heating the forearm skin from a baseline of 33 to 42 oC at a rate of 0.1oC/1s. The purpose of this study was to test two different heating protocols from the standard heating protocol. The first heating protocol decreased the target temperature to 39oC compared to the standard heating protocol. The second heating protocol used gradual heating rate of 0.1oC/60s compared to the standard heating proto- col. Four microdialysis fibers were placed in the forearm skin of 16 young healthy subjects. In protocol 1 and 2 (female = 8, male = 8): (1) Control, (2) NO inhibitor, L-NAME (3) KCa channel inhibitor, tetraethylammonium (TEA), and (4) L-NAME +TEA . For both studies, skin sites were locally heated on the forearm from a baseline of 33oC to target temperatures. After maintaining the target temperature for about 40 minutes, the four skin sites were heated to 43.5oC to attain maximal skin blood flow (SkBF). SkBF was measured with Laser Doppler flowmetry. Data are presented as % maximal cutaneous vascular conductance (CVC), which equals blood flow divided by mean arterial pressure. In protocol 1, all drug sites attenuated plateau CVC from the control sites. Compared to the control plateau CVC, there was 80.1 % decrease with L-NAME, close to 77.6% decrease in the L-NAME +TEA site, and 35.2% decrease with TEA. In protocol 2, L-NAME and L-NAME + TEA sites showed attenuated plateau CVC, 29.1% and 32.2% decrease, respectively, compared to the control site.

Effects of Chronic Passive Heating on Resting Heart Rate, Blood Pressure, and Body Core Temperature

Presenter: Kaitlin Livingston

Mentors: Christopher Minson and Vienna Brunt, Human Physiology

Poster: 44

Major: Human Physiology 

Repeated bouts of exercise in the heat are known to decrease resting body core temperature (Tc), mean arterial pressure (MAP) and resting heart rate (HR). Although exercise in the heat produces these cardiovascular changes, it is currently unknown whether passive chronic heating provides the same benefits. Our research sought to examine the effects of passive chronic heating on resting Tc, MAP, and HR. Five sedentary, college-aged subjects (4 females, 1 male) were assigned to an 8-week hot water immersion program (4-5 sessions/week). Subjects were submerged to the clavicle in 40.5°C water until a rectal temperature (Tre) of 38.5°C was reached. Subjects maintained a Tre between 38.5-39.0°C during an hour of partial immersion. HR and Tre were measured with a HR monitor and rectal thermistor both at rest and at 5-minute intervals during the heat stress. MAP was measured on another day with brachial auscultation after ≥20 minutes of supine rest. Both resting MAP (81±1 vs. 76±2 mmHg, p=0.02) and resting Tre (37.4±0.5 vs. 36.8±0.4°C, p=0.03) decreased after 8 weeks of passive heat stress with no change in resting HR (63±5 vs. 63±6 beats/min, p=0.26). Chronic passive heat stress reduces resting MAP and Tre similarly to what is observed with exercise heat in the heat. This suggests that chronic passive heat stress could be used to benefit cardiovascular health similarly to exercise in the heat.

The Effect of Chronic Passive Heat Therapy on Forearm Reactive Hyperemia

Presenter: Andrew Jeckell

Mentors: Christopher Minson and Vienna Brunt, Human Physiology

Poster: 31

Major: Post-baccalaureate 

Reactive hyperemia is a transient increase in blood flow that occurs following a period of ischemia (e.g. arterial occlusion) and is indicative of microvascular health. Regular exercise is a critical preventive measure in maintaining reactive hyperemia; however, consistent exercise is difficult or impossible for some people. Recent evidence suggests chronic passive heat therapy (CHT) may result in improvements to cardiovascular health similar to exercise. To examine the effects of 8 weeks of CHT on forearm post-occlusive reactive hyperemia, six healthy university students (21 ± 1 years) underwent hot water immersion 4-5 times per week to maintained rectal temperature of 38.5°C
for 1 hour per session. Before and after 8 weeks of CHT, brachial artery blood flow was measured via Doppler ultrasonography for 3 minutes following a 5-minute forearm arterial occlusion. Data presented as mean ± SE vascular conductance (VC, blood flow divided by mean arterial pressure). In preliminary subjects, change in peak VC from baseline, indicating structural microvascular changes, increased following CHT from 1.77 ± 0.24 to 2.26 ± 0.20 ml/ min/mmHg (p = 0.09). Area-under-the-curve of the hyperemic response, indicating functional changes, increased from 59.7 ± 9.0 to 111.9 ± 13.0 sec.ml/min/mmHg (p = 0.11). CHT appears to produce structural and functional microvasculature changes comparable to that of exercise, and could potentially serve as an alternative method for improving cardiovascular health.

Chronic Passive Heat Therapy Improves Microvascular Nitric Oxide-Dependent Dilation during Skin Local Heating

Presenter: Taylor Eymann

Mentors: Christopher Minson and Vienna Brunt, Human Physiology

Poster: 21

Major: Human Physiology

Vascular dysfunction, often caused by deficient nitric oxide (NO) production, is present in the majority of cardiovascular disease and is first detectible in the microcirculation. Heat stress can increase NO production via
heat shock protein expression. Therefore chronic passive heat therapy (CHT) may improve microvascular health
and lower cardiovascular risk. The cutaneous circulation is easily accessible and represents overall microvascular health. PURPOSE: To observe the effects of 8wks of CHT on cutaneous NO-dependent dilation. METHODS: Seven healthy, sedentary subjects were immersed in either 40.5°C (N=5; CHT) or 36.5°C (N=2; sham group) water for 90min 4-5 times per week for 8 weeks. Before and after the 8wks, two intradermal microdialysis fibers were inserted into the forearm and infused with lactated Ringer’s solution (control) and a nitric oxide synthase competitive inhibitor (L-NNA), to inhibit NO synthase. Increased skin blood flow responding to local skin heating to 39°C, which is a test of microvascular health, was measured at each site using laser-Doppler flowmetry. NO-dependent dilation, calculated as the difference between control and L-NNA sites, was expressed as percent maximal cutaneous vascular conductance (%CVCmax; flow/mean arterial pressure). RESULTS: CHT increased NO-dependent dilation from 27±4 to 36±5%CVCmax (p<0.05). No improvement was observed in sham subjects. CONCLUSION: Our findings suggest heat therapy increases NO production and vasodilation in the human microcirculation. Continued exposure to passive heat may lower cardiovascular risk.

In Vitro Angiogenesis Increases with Chronic Passive Heat Therapy: Likely Mechanism for Improved Cardiovascular Health

Presenter: Lindan Comrada

Mentors: Christopher Minson and Vienna Brunt, Human Physiology

Poster: 14

Major: Biochemistry

Chronic passive heat therapy (CHT) shows exciting potential for improving cardiovascular health and overall quality of life. Angiogenesis occurs naturally when endothelial cells lining the inside of blood vessels proliferate and reorganize into new vasculature. Heat stress induces expression of many factors that promote angiogenesis which can decrease blood pressure. CHT may therefore be an effective means of increasing vascularization and improving vascular health. Angiogenesis can be assessed easily and non-invasively by using an in vitro endothelial tubule formation bioassay. PURPOSE: To determine if acute heating and/or chronic passive heating has a positive effect on in vitro endothelial tubule formation. METHODS: Six sedentary, healthy individuals (aged 22±1 yrs) were subjected to 8 weeks of heating via hot tub (40.5°C) 4-5 times per week for 36 sessions. During each session, rectal temperature was increased and maintained at ≥38.5°C for 60 minutes. Blood samples were collected into serum separating vacutainers before and after each heating session at weeks 0 and 8. Two in vitro angiogenesis bioassays were performed for each sample by plating cultured human umbilical vein endothelial cells (HUVECs) onto Matrigel and treating with serum from subjects. After 10 hours of incubation, tubule formation per frame was determined using phase-contrast microscopy at 2.5X magnification by two blinded experimenters using ImageJ software and results were averaged. RESULTS: Total tubule length increased after 8 weeks of CHT from 71.7±1.4 to 75.5±1.6 mm/frame (p=0.02), and tended to increase with acute heating to 74.2±1.5 mm/frame (p=0.19). CONCLUSION: Heat therapy increases the capacity for angiogenesis both acutely (single heat exposure) and chronically, suggesting CHT improves vascular health. CHT is simple enough to be used by many patient populations with little or no supervision and may be an effective means of improving cardiovascular health and therefore quality of life.

Acute Hemodynamic Adjustments to Hot Water Immersion

Presenter: Sarianna Harris

Faculty Mentor: Christopher Minson, Brett Ely

Presentation Type: Poster 67

Primary Research Area: Science

Major: Human Physiology

Funding Source: Clark Honor’s College Thesis Research Grant, $1,000; Undergraduate Research Opportunity Program’s Mini Grant Recipient, $1,000

Passive heat therapy (regular hot tub or sauna use) has gained attention for its potential to improve cardiovascular health, and recent evidence suggests that it produces beneficial vascular adaptations. However, the cardiovascular responses to a single bout of hot water immersion have not yet been characterized; therefore the mechanisms that produce long-term adaptations are not yet fully known. PURPOSE: To examine the acute cardiovascular hemodynamic effects of a 60min bout of hot water immersion. METHODS: Thirteen healthy, young (26±4 yrs) subjects were immersed to heart level in 40.5°C water for 60minutes. Measurements, including heart rate, cardiac output, and skin blood flow, as well as diameter and blood velocity of carotid and brachial arteries, were taken at baseline prior to and during immersion. Peak changes were compared to baseline. RESULTS: Heart rate increased significantly from 60±3 at baseline to a peak of 121±5 bpm during immersion. Cardiac output increased significantly from baseline to peak, as did blood flow in both carotid and brachial arteries, total shear (4*velocity/diameter) in both brachial and carotid arteries, and skin blood flow. CONCLUSION: Hot water immersion caused substantial increases in cardiac output, arterial blood flow, skin blood flow, and shear rates. These changes are similar to those seen during a single bout of exercise, suggesting that repeated hot water immersion may cause beneficial vascular adaptations through similar mechanisms.

Hemodynamics of Post-Exercise and Post-Passive Heat Stress Recovery Periods

Presenter(s): Cameron Colbert

Faculty Mentor(s): Christopher Minson & Michael Francisco

Oral Session 4 CQ

Recent research suggests that individuals exposed to heat stress chronically (e.g. sauna users) enjoy similar benefits as chronic exercisers. Many of exercise’s benefits are facilitated during the recovery phase, or the period of time following the cessation of exercise. By studying the cardiovascular responses during the recovery period following both heat stress and exercise, we can further explore clinically-relevant applications of heat therapy. This study seeks to compare the acute physiology of the recovery periods following exercise and hot water immersion (HWI). METHODS: 9 subjects (4 F, 5 M, age 22.4 ± 2.4 years) in random order exercised for 60 minutes at 60% VO2 peak and were immersed in 40.5oC water for 60 minutes on separate days. Measurements were made at baseline, during the interventions, and for 60 minute recovery period following both interventions. Heart rate, blood pressure, core temperature, and subjective measures were recorded every five minutes. Cardiac output, femoral and brachial artery hemodynamics were assessed using Doppler ultrasonography every 20 minutes. Skin blood flow was measured continuously during recovery. RESULTS: Brachial artery antegrade shear rate increased during HWI to a greater extent than exercise (p0.06). Skin blood flow following hot water immersion was significantly greater than that of post-exercise for the first 35 minutes of recovery (p<0.028). DISCUSSION: Many of the changes seen during the post-exercise recovery period that lead to beneficial cardiovascular adaptation are also seen during the post- immersion recovery period, suggesting hot water immersion may improve cardiovascular health.