Geert Kleinnibbelink

Chapter 3 70 a motorized treadmill at 3,000m simulated altitude (equivalent to FiO 2 14.5%) at high- intensity (85% of maximal heart rate). Environmentalchamberandsafety .All trainingsessionswereconductedinanenvironmental chamber (TISS, Alton, UK; Sportingedge, Bastingstoke, UK), whichwas set-up by a qualified technician. 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. Acute mountain sickness symptoms (AMS, measured by Lake Louise Score (LLS) 16 ) were monitored during testing and training sessions every 20 minutes. Subjects were removed from the environmental chamber if oxygen saturation levels dropped below 75% or severe AMS was suspected (LLS ≥ 6). Echocardiographic measurements Echocardiographic assessments, prior to and post training program, were performed at rest (‘rest’) and during recumbent cycling to elevate heart rate allowing direct assessment of cardiac function during exercise (‘stress’, target HR 110-120 bpm). Rest and stress echocardiography were performed in the left lateral decubitus position on a supine cycle ergometer (Lode B.V.; Groningen, The Netherlands). For stress echocardiography, low-to-moderate-intensity exercise consisted of recumbent cycling at a cadence of ~60 revolutions per minute. All examinations were performed by one highly experienced sonographer (DO) using a Vivid E95 ultrasound machine (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 was performed by a single observer with experience in echocardiography (GK) using three consecutive stored cycles with exception of strain-volume loops which were analyzed from a single cardiac cycle. The observer was blinded for the timing (pre vs . post) under which echocardiography was performed. Conventional measurements . Cardiac structural and functional measurements at rest and during low-to-moderateexerciseweremadeaccording to the current guidelines for cardiac