scholarly journals Acetazolamide reduces exercise capacity and increases leg fatigue under hypoxic conditions

2003 ◽  
Vol 94 (3) ◽  
pp. 991-996 ◽  
Author(s):  
Luke A. Garske ◽  
Michael G. Brown ◽  
Stephen C. Morrison
Keyword(s):  
Exercise Capacity ◽  
Ventilatory Response ◽  
Acute Mountain Sickness ◽  
Peak Exercise ◽  
Double Blind ◽  
Ventilatory Responses ◽  
Hypoxic Conditions ◽  
Mountain Sickness ◽  
Randomized Crossover Study ◽  
Hypoxic Exercise

Acetazolamide (Acz) is used at altitude to prevent acute mountain sickness, but its effect on exercise capacity under hypoxic conditions is uncertain. Nine healthy men completed this double-blind, randomized, crossover study. All subjects underwent incremental exercise to exhaustion with an inspired O2 fraction of 0.13, hypoxic ventilatory responses, and hypercapnic ventilatory responses after Acz (500 mg twice daily for 5 doses) and placebo. Maximum power of 203 ± 38 (SD) W on Acz was less than the placebo value of 225 ± 40 W ( P < 0.01). At peak exercise, arterialized capillary pH was lower and Po 2 higher on Acz ( P < 0.01). Ventilation was 118.6 ± 20.0 l/min at the maximal power on Acz and 102.4 ± 20.7 l/min at the same power on placebo ( P < 0.02), and Borg score for leg fatigue was increased on Acz ( P < 0.02), with no difference in Borg score for dyspnea. Hypercapnic ventilatory response on Acz was greater ( P < 0.02), whereas hypoxic ventilatory response was unchanged. During hypoxic exercise, Acz reduced exercise capacity associated with increased perception of leg fatigue. Despite increased ventilation, dyspnea was not increased.

No Evidence of Cerebral Oedema in Severe Acute Mountain Sickness

Cephalalgia ◽  
2004 ◽  
Vol 24 (1) ◽  
pp. 66-71 ◽  
Author(s):  
R Fischer ◽  
C Vollmar ◽  
M Thiere ◽  
C Born ◽  
M Leitl ◽  
...  
Keyword(s):  
Cerebral Oedema ◽  
Acute Mountain Sickness ◽  
Diffusion Weighted Mri ◽  
Double Blind ◽  
Altitude Exposure ◽  
Hypoxic Conditions ◽  
Mountain Sickness ◽  
Almost All ◽  
Magnetic Resonances ◽  
And Diffusion

In a randomized, double-blind cross-over study 10 subjects were exposed to a simulated altitude of 4500 m for 10 h after administration of placebo, acetozolamide (250 mg bid) or theophylline (250 mg bid). T2-weighted magnetic resonances images (MRI) and diffusion weighted MRI were obtained directly after exposure to altitude under hypoxic conditions. Although eight of 10 subjects had moderate to severe acute mountain sickness (AMS), we found no evidence of cerebral oedema, irrespective of the medication taken. Almost all subjects showed a decrease in inner cerebrospinal fluid (iCSF) volumes (placebo −10.3%, P = 0.02; acetazolamide −13.2%, P = 0.008, theophylline −12.2%, n.s.). There was no correlation between AMS symptoms and fluid shift. However, we found a significantly positive correlation of large (>10 ml) iCSF volume and more severe AMS after administration of placebo ( r = 0.76, P = 0.01). Moderate to severe AMS after high altitude exposure for 10 h is associated with a decreased iCSF-volume independent of AMS severity or medication without signs of cerebral oedema.

scholarly journals Acetazolamide reduces exercise capacity following a 5-day ascent to 4559 m in a randomised study

2018 ◽  
Vol 4 (1) ◽  
pp. e000302 ◽  
Author(s):  
Arthur R Bradwell ◽  
Kimberley Ashdown ◽  
Carla Rue ◽  
John Delamere ◽  
Owen D Thomas ◽  
...  
Keyword(s):  
Heart Rate ◽  
Exercise Capacity ◽  
Acute Mountain Sickness ◽  
Bicycle Ergometer ◽  
Older Individuals ◽  
Double Blind ◽  
Randomised Study ◽  
Age Related ◽  
Mountain Sickness ◽  
Gas Measurements

ObjectiveTo assess whether acetazolamide (Az), used prophylactically for acute mountain sickness (AMS), alters exercise capacity at high altitude.MethodsAz (500 mg daily) or placebo was administered to 20 healthy adults (aged 36±20 years, range 21–77), who were paired for age, sex, AMS susceptibility and weight, in a double-blind, randomised manner. Participants ascended over 5 days to 4559 m, then exercised to exhaustion on a bicycle ergometer, while recording breath-by-breath gas measurements. Comparisons between groups and matched pairs were done via Mann-Whitney U and Pearson’s χ2tests, respectively.ResultsComparing paired individuals at altitude, those on Az had greater reductions in maximum power output (Pmax) as a percentage of sea-level values (65±14.1 vs 76.6±7.4 (placebo); P=0.007), lower VO2max(20.7±5.2 vs 24.6±5.1 mL/kg/min; P<0.01), smaller changes from rest to Pmaxfor VO2(9.8±6.2 vs 13.8±4.9 mL/kg/min; P=0.04) and lower heart rate at Pmax(154±25 vs 167±16, P<0.01) compared with their placebo-treated partners. Correlational analysis (Pearson’s) indicated that with increasing age Pmax(r=−0.83: P<0.005) and heart rate at Pmax(r=−0.71, P=0.01) reduced more in those taking Az.ConclusionMaximum exercise performance at altitude was reduced more in subjects taking Az compared with placebo, particularly in older individuals. The age-related effect may reflect higher tissue concentrations of Az due to reduced renal excretion. Future studies should explore the effectiveness of smaller Az doses (eg, 250 mg daily or less) in older individuals to optimise the altitude–Az–exercise relationships.

Effect of acetazolamide on normoxic and hypoxic exercise in humans at sea level

1983 ◽  
Vol 55 (6) ◽  
pp. 1772-1776 ◽  
Author(s):  
R. B. Schoene ◽  
P. W. Bates ◽  
E. B. Larson ◽  
D. J. Pierson
Keyword(s):  
Carbonic Anhydrase ◽  
Minute Ventilation ◽  
Acute Mountain Sickness ◽  
Bicycle Ergometer ◽  
Double Blind ◽  
Chronic Mountain Sickness ◽  
Hemoglobin Saturation ◽  
Mountain Sickness ◽  
Exercise In Humans ◽  
Hypoxic Exercise

Acetazolamide (A) is a potent inhibitor of carbonic anhydrase. It has been shown to be efficacious in preventing acute mountain sickness as well as decreasing the O2 desaturation that occurs during sleep in individuals with chronic mountain sickness who live at altitude. Very little data, however, are available about its effect on exercise. We studied six healthy males in a double-blind cross-over design using acetazolamide and placebo (P) during normoxic and hypoxic (fractional inspired O2 = 0.118) progressive work exercise to exhaustion on a bicycle ergometer. A metabolic acidosis was documented in all subjects on A (P less than 0.045). Before exercise, subjects on A had 2.0 and 3.5 l/min increase in minute ventilation (VE) during normoxia (P = not significant) and hypoxia (P less than 0.005), respectively, and a 2.2% increase in arterialized O2 hemoglobin saturation (SaO2) during hypoxia. During normoxic and hypoxic exercise, VE/kpm and SaO2/kpm were significantly higher while the respiratory exchange ratio (R) was significantly lower on A. These effects were greater on hypoxia. During normoxia, maximal O2 consumption (1/min) was lower on A [3.1 +/- 0.4 (A) vs. 3.8 +/- 0.2 (P), P less than 0.025] and higher during hypoxia on A[2.6 +/- 0.7 (A) vs. 2.4 +/- 0.1 (P), P less than 0.05]. The increase in exercise VE on A may result in an increased alveolar and subsequent arterial O2 tension which may be important for exercise at altitude. Carbonic anhydrase inhibition may also affect CO2 transport in the lung, which may explain the lower R.

scholarly journals Acetazolamide reduces exercise capacity following a five-day ascent to 4559 m on Monte Rosa

2017 ◽  
Author(s):  
Arthur R. Bradwell ◽  
Kimberly Ashdown ◽  
Carla Gallagher ◽  
John Delamere ◽  
Owen D. Thomas ◽  
...  
Keyword(s):  
Exercise Capacity ◽  
Minute Ventilation ◽  
Acute Mountain Sickness ◽  
Bicycle Ergometer ◽  
Gas Analysis ◽  
Base Line ◽  
Older Individuals ◽  
Double Blind ◽  
Age Related ◽  
End Tidal

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.

Sumatriptan reduces exercise capacity in healthy males: a peripheral effect of 5-hydroxytryptamine agonism?

2000 ◽  
Vol 98 (6) ◽  
pp. 643-648 ◽  
Author(s):  
Gerald P. MCCANN ◽  
Helen CAHILL ◽  
Stephen KNIPE ◽  
Douglas F. MUIR ◽  
Paul D. MACINTYRE ◽  
...  
Keyword(s):  
Heart Rate ◽  
Oxygen Consumption ◽  
Exercise Capacity ◽  
Gas Analysis ◽  
Peak Oxygen Consumption ◽  
Peak Exercise ◽  
Double Blind ◽  
Peripheral Effect ◽  
Expired Gas Analysis ◽  
Exercise Induced

5-Hydroxytryptamine (5-HT; serotonin) has been implicated in the perception of exercise-induced fatigue. Sumatriptan is a selective 5-HT1B/D receptor agonist which does not cross the blood–brain barrier. The aim of the present study was to determine the effect of sumatriptan on exercise capacity. Ten healthy male subjects (mean age 28.4±10.8 years) performed a maximal treadmill exercise test according to the Bruce protocol with expired gas analysis on two occasions. Either 6 mg of sumatriptan or placebo was administered subcutaneously in a randomized, double-blind, placebo-controlled, cross-over design. Exercise time was greater after placebo compared with sumatriptan [914 and 879 s respectively; 95% confidence interval (CI) of difference 12.1 s, 59.1 s; P = 0.008]. There was no significant effect on peak oxygen consumption (placebo, 50.6±6.3 ml·min-1·kg-1; sumatriptan, 51.7±7.6 ml·min-1·kg-1). Sumatriptan administration resulted in decreases in both heart rate (sumatriptan, 188±14 beats/min, placebo, 196±12 beats/min; 95% CI of difference 12.6, 2.6; P = 0.008) and respiratory exchange ratio (sumatriptan, 1.23±0.06; placebo, 1.26±0.07; 95% CI of difference 0.05, 0.01; P = 0.01) at peak exercise. There were no significant differences in blood pressure, heart rate or submaximal oxygen consumption between sumatriptan and placebo treatments at any stage of exercise. Thus sumatriptan reduces maximal exercise capacity in normal males. The failure to demonstrate any haemodynamic or cardiorespiratory effect suggests that sumatriptan enhances perception of fatigue by a peripheral mechanism affecting 5-HT modulation.

Hypoxic Ventilatory Response, Ventilation, Gas Exchange, and Fluid Balance in Acute Mountain Sickness

2002 ◽  
Vol 3 (4) ◽  
pp. 361-376 ◽  
Author(s):  
Peter Bärtsch ◽  
Erik R. Swenson ◽  
André Paul ◽  
Bernhard Jülg ◽  
Elke Hohenhaus
Keyword(s):  
Gas Exchange ◽  
Fluid Balance ◽  
Ventilatory Response ◽  
Acute Mountain Sickness ◽  
Hypoxic Ventilatory Response ◽  
Mountain Sickness
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