The influence of amitriptyline on human thermoregulation in young healthy adults

INTERVENTION: Participants will be asked to complete a humidity ramp heat stress test 7 hours after oral ingestion of a single dose of 75 mg amitriptyline hydrochloride or placebo. All participants will complete two trials, one with amitriptyline hydrochloride and one with placebo in a cross‐over design with a wash‐out period between treatments of at least 7 days. Ingestion of the drug/placebo will occur onsite and will be monitored by research staff. The heat stress test involves participants being asked to remain seated while exposed to 43°C, 20% relative humidity (RH) for 30 minutes before a stepwise increase in relative humidity occurs (4% every 8 min until 64% RH). The heating protocol is a standard methodological approach within the field of human thermoregulation. The total duration of the heat stress test is 118min. The heat stress test is carried out in a climate‐controlled chamber at the research clinic and monitored by research staff. CONDITION: Cardiovascular ‐ Normal development and function of the cardiovascular system Heat related thermal strain;Heat related cardiovascular strain;Heat related changes in thermal perceptions (i.e., comfort and sensation); ; Heat related thermal strain ; Heat related cardiovascular strain ; Heat related changes in thermal perceptions (i.e., comfort and sensation) Injuries and Accidents ‐ Other injuries and accidents Neurological ‐ Studies of the normal brain and nervous system Public Health ‐ Other public health PRIMARY OUTCOME: Critical relative humidity at which an inflection in rectal temperature is observed[Measured environmental conditions in the climate‐controlled chamber and a thin, flexible temperature probe self‐inserted 10‐12 cm into the participants' rectum for rectal temperature. The "critical" relative humidity is when an inflection in rectal temperature is observed during the ramp.] SECONDARY OUTCOME: Activated sweat gland density ; [Iodine soaked cotton paper (9 cm^2) will be applied to the skin surface at the upper back for a period of 3‐5 seconds intermittently throughout the exposure. This will reveal each individual sweat gland that is active in the area of application allowing the subsequent estimation of active sweat glands (glands/cm^2). Sweat gland density will be measured at 94min and 118min during the heat stress test] Change in heart rate[Absolute heart rate (beats per minute) will be continuously recorded via chest strap monitor. Change from minimum to maximum heart rate recorded during the heat stress test] Change in rectal temperature[A thin, flexible temperature probe self‐inserted 10‐12 cm into the participants' rectum. Change from minimum to maximum rectal temperature recorded during the heat stress test] Critical relative humidity at which an inflection in heart rate is observed[Measured environmental conditions in the climate‐controlled chamber and a chest strap monitor for heart rare The "critical" relative humidity is when an inflection in heart rate is observed during the ramp.] Heart Rate (absolute)[Absolute heart rate (beats per minute) will be continuously recorded via chest strap monitor. At end of baseline (30min) and every 16 min points, 38 to 118 min during the heat stress test] Local sweat rate[Local sweat rate will be measured continuously during the study visits using a plastic capsule attached to the skin surface and ventilated with dry air on the chest and the forearm At end of baseline (30min) and every 16 min points, 38 to 118 min during the heat stress test] Perceptual rating of whole‐body thermal discomfort[Thermal discomfort will be monitored via a four‐point visual analogue scale which ranges from not uncomfortable (1) to very uncomfortable (4). This outcome will indicate the thermal acceptability of the environment/ intervention combination. At the end of baseline (30min) and every 16 min points, 38 to 118 min during the heat stress test.] Perceptual rating of whole‐body thermal sensation[Using a 100 mm visual analogue scale participants will rate their whole body thermal sensation from neutral (0 mm) to very hot (100 mm) providing inside into their perception of their thermal environment as well as the influence of the intervention on this perception. At the end of baseline (30min) and every 16 min points, 38 to 118 min during the heat stress test.] Rate pressure product[The product of systolic blood pressure (measured via an automated blood pressure cuff) and heart rate (measured via a chest strap monitor) will be calculated and taken as an inde Xof myocardial oxygen consumption, and hence cardiovascular strain (mmHg/bpm). At end of baseline (30min) and every 16 min points, 38 to 118 min during the heat stress test] Rectal Temperature[A thin, flexible temperature probe self‐inserted 10‐12 cm into the participants' rectum. At end of baseline (30min) and every 16 min points, 38 to 118 min during the heat stress test] Skin blood flow ; [A laser doppler flowmetry (LDF) unit will be secured to the chest and the forearm of the participant and used to monitor cutaneous blood flow. At end of baseline (30min) and every 16 min points, 38 to 118 min during the heat stress test] Thirst perception[Participants will be asked to rate their thirst, mouth dryness and how pleasant a drink of water would be on three separate visual analogue scales. These scales are each 100 mm long and the participant may mark anywhere on the line, with a score between 0‐100 being determined for each. These three scores will be taken as an indication of the participants level of thirst throughout the exposure. At the end of baseline (30min) and every 16 min points, 38 to 118 min during the heat stress test.] Whole body sweat rate/ loss ; [Nude body mass will be measured on a platform scale to calculate sweating output (g/h). ; Body mass measurements will take place at the beginning and end of each heat stress test.] INCLUSION CRITERIA: 1. Between the ages of 18‐40 years 2. Able to understand the demands of the protocol, has had any questions answered and has voluntarily signed the participant consent form prior to any study procedures 3. In good health, a non‐smoker, with no history of respiratory, metabolic, cardiovascular, blood pressure disease or diabetes and not currently taking any medication 4. Cleared for participation from licenced medical professional