Geert Kleinnibbelink

Exercise-Induced Cardiac Function under Hypoxia 2 41 (HP Cosmos, Nussdorf, Germany) and 60 minutes of recovery in seated position. HR was measured continuously throughout (Polar, Kempele, Finland), and rate of perceived exertion (RPE) was monitored during the 45-minutes high-intensity running exercise. 31 In total four echocardiographic assessments were performed per test day. After acclimation and prior to the 45-minute exercise, echocardiography was performed under resting conditions (‘rest’) and during recumbent cycling to elevate heart rate to directly assess cardiac function during exercise (‘stress’, target HR 110-120 bpm). The ‘stress’ echocardiogram was repeated directly after the 45-minute exercise, to prevent sympathetic withdrawal (i.e. a drop in BP and HR). 32 Finally, images were obtained at the end of the 60 minutes of recovery in a resting state. During every echocardiography assessment, BP measurements were performed. Measurements were performed at the same time on both days to control for diurnal variation. Fluid intake was controlled by providing the same amount of water to participants during both testing days. Environmental chamber and safety . All exercise tests were conducted in an environmental chamber (TISS, Alton, UK; Sportingedge, Basingstoke, UK). Normobaric hypoxia was achieved by a nitrogen dilution technique. Ambient temperature, carbon dioxide (CO 2 ) and oxygen (O 2 ) levels were controlled in all sessions (20°C; FiO 2 14.5%; CO 2 0.03%), whilst a Servomex gas analysis system (Servomex MiniMP 5200, Servomex Group Ltd., UK) was used inside the chamber to provide the researcher continuous information regarding O 2 and CO 2 levels. Acutemountain sickness symptoms (AMS, measured by Lake Louise Score 33 (LLS)) were monitored during testing and training sessions every 20 minutes. The subject was removed from the environmental chamber if oxygen saturation levels dropped below 80% or severe AMS was suspected (LLS ≥ 6). Echocardiographic measurements Rest and stress echocardiography were performed in the left lateral decubitus position on a supine cycle ergometer (Lode B.V.; Groningen, The Netherlands) by one highly experienced sonographer (DO) using a Vivid E95 ultrasoundmachine (GE Medical, Horton, Norway), equipped with a 1.5-4.5 MHz transducer. Images were stored in raw digital imaging and communication in medicine (DICOM) format and were exported to an offline workstation (EchoPac, version 203, GE Medical, Horton, Norway). Data-analysis, from three

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