RT Journal Article SR Electronic T1 Acetazolamide reduces exercise capacity following a five-day ascent to 4559 m on Monte Rosa JF bioRxiv FD Cold Spring Harbor Laboratory SP 105726 DO 10.1101/105726 A1 Arthur R. Bradwell A1 Kimberly Ashdown A1 Carla Gallagher A1 John Delamere A1 Owen D. Thomas A1 Samuel J.E. Lucas A1 Alex D. Wright A1 Stephen J. Harris A1 Stephen D. Myers A1 Birmingham Medical Research Expeditionary Society YR 2017 UL http://biorxiv.org/content/early/2017/02/03/105726.abstract AB Acetazolamide (Az) is widely used to prevent and treat the symptoms of acute mountain sickness (AMS) but whether it alters exercise capacity at high altitude is unclear. Az (250 mg twice daily) or placebo were administered to 20 healthy adults (age range, 21-77 years) in a double-blind, randomized manner. Participants ascended over five days to 4559 m, before undertaking an incremental exercise test to exhaustion on a bicycle ergometer, with breath-by-breath gas measurements recorded using a portable gas analysis system. Maximum power output (Pmax) was reduced on Az compared with placebo (p=0.03), as was maximum O2 uptake (VO2max) (20.7 vs 24.6 mL/kg/min; p=0.06) and maximum expired CO2 (VCO2max) (23.4 vs 29.5 mL/kg/min; p=0.01). Comparing individuals matched for similar characteristics, Az-treated participants had smaller changes than placebo-treated participants in minute ventilation (88 vs 116 L/min: p=0.05), end tidal O2 (6.6 vs 9.3 mm Hg: p=0.009), end-tidal CO2 (−2.3 vs −4.2 mm Hg: p=0.005), VO2max (9.8 vs 13.8 mL/kg/min; p=0.04) and VCO2max (14.7 vs 20.8 mL/kg/min; p=0.009). There was a negative correlation between the mean ages of paired vs placebo-treated individuals and differences in Pmax reductions from base-line to altitude (r =−0.83: p<0.005) and HRmax at altitude (r=−0.71; p=0.01). Glomerular filtration rate (measured at sea-level) declined with increasing age (r=−0.69; p=0.001). Thus, 250mg of Az twice daily reduced exercise performance, particularly in older individuals. The age-related effects of Az may reflect higher tissue concentrations due to reduced drug clearance in older people.