Influence of Exercise Training on Chemoreflex Sensitivity in healthy adult humans.

This is a non-therapeutic mechanistic physiological study. All of the following procedures will be conducted by the doctoral candidate under supervision of a trained human physiologist staff member. The laboratory where all assessments will take place is located at the Exercise Nutrition and Metabolism Laboratory, Department of Exercise Sciences, Newmarket Campus, University of Auckland. All participants will undergo an initial visit to the laboratory where screening and familiarisation with all study protocol will take place. This visit will be 60 minutes duration, and an investigator will explain the nature of the study procedures, answer any questions, and obtain written informed consent from the participant. Anthropometric (height, weight), demographic, general health, physical activity readiness (Get Active questionnaire) and physical activity information will be obtained. Participants will then perform a handgrip strength test to enable classification of participants by strength (resistance training assessment) and a graded maximal exercise test to categorise participants according to their aerobic capacity (endurance training assessment). During the handgrip strength test participants will use their dominant hand to maximally squeeze the dynamometer, with the highest of three trials obtained as the final value. During the graded maximal exercise test, participants will be instrumented with a heart rate monitor, mouthpiece and headset attached to a two-way valve with a room air inlet and outlet to a hose connected to a metabolic cart gas analysis system. Participants will perform 5-minute warm up at a self-selected pace, followed by a 3-minute adjustment period to determine the participant’s optimal speed for the duration of the maximal exercise test. The selected speed will remain constant for the duration of the test, with the gradient of the motorized treadmill increasing by 1% every 1 minute, beginning at 0%. The second visit will be an experimental session. This visit will be scheduled ~2-7 days after the initial familiarisation/screening visit, as appropriate. However, premenopausal women will be studied during the first five days of their menstrual cycle (early follicular phase) or during the placebo/no-hormone phase of oral contraceptive use, as appropriate. This visit will be 90 minutes duration. At the experimental session, participants will be asked to sit in a comfortable armchair and remain in that position throughout the session. Participants will be instrumented for continuous monitoring of blood pressure, heart rate, respiration and brain blood flow. More specifically, beat-to-beat blood pressure will be measured using finger photoplethysmography, using a small lightweight cuff wrapped around the finger and a cuff wrapped around the upper arm for calibration. Heart rate will be measured using standard electrocardiogram involving the placement of 3 sticky electrodes on the collarbones and chest (standard 3 lead ECG). Participants will wear a mouthpiece and nose clip to monitor respiration. Brain blood flow will be monitored using a transcranial Doppler ultrasound, with a probe placed over the temporal ‘window’ in front of the ear and above the zygomatic arch. The probe will be fixed in place using an adjustable headband and small amount of ultrasound gel. After instrumentation, a 15 minute resting baseline will be observed with the last 5 minutes used for analysis, followed by chemoreflex assessment. Chemoreflex assessment will involve two breathing tests. Tests are separated by a 15 minute rest period. The first test is isocapnic hypoxia (10% O2-90% N2), used to evaluate peripheral chemoreflex stimulation. The exposure will last 5 minutes, with end tidal oxygen of ~45mmHg and end tidal carbon dioxide of ~40mmHg maintained throughout the test. The second test is hyperoxic hypercapnia (CO2 rebreathing), used to evaluate central chemoreflex stimulation with diminished peripheral chemoreflex stimulation). The participant will then be coached using a metronome and verbal feedback to hyperventilate in room air, until attaining an end tidal carbon dioxide concentration of ~25mmHg. Upon reaching this, the participant will be asked to perform a maximal expiration below functional residual capacity. Upon completion, the inspiratory source will be switched to a rebreathing bag filled with ~95% O2-~5% CO2, and the participant will be instructed to perform 5-6 deep and rapid breaths. Following this, the participant will be instructed to breath as required, until their end tidal carbon dioxide reaches ~55mmHg, signalling the end of the test.