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.

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 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.

Cationic concentrations and transmembrane fluxes in erythrocytes of humans during exercise

1986 ◽  
Vol 61 (1) ◽  
pp. 37-43 ◽  
Author(s):  
P. Hespel ◽  
P. Lijnen ◽  
R. Fiocchi ◽  
B. Denys ◽  
W. Lissens ◽  
...  
Keyword(s):  
Exercise Capacity ◽  
Maximal Exercise ◽  
Potassium Concentration ◽  
Work Load ◽  
Bicycle Ergometer ◽  
Normal Male ◽  
Base Line ◽  
Initial Work ◽  
Severe Exercise ◽  
Maximal Exercise Capacity

The effect of exercise on the intraerythrocyte cationic concentrations and transmembrane fluxes such as the Na+-K+-adenosinetriphosphatase (ATPase) pump, the Na+-K+ cotransport, and the Na+-Li+ countertransport system was studied in 11 normal male volunteers. All subjects performed an uninterrupted incremental exercise test on a bicycle ergometer, starting at an initial work load of 20% of the subjects' maximal exercise capacity, as determined in a pretest. The work rate was increased with an additional 20% each 6 min up to a final work load of 80%. Blood samples were taken at rest, at 60 and 80% of maximal exercise capacity, and 1, 2, 3, 4, 5, and 30 min after cessation of exercise. At moderate exercise (60% of maximal exercise capacity) the intraerythrocyte potassium concentration was not changed, but at severe exercise (80% of maximal exercise capacity) it was decreased. After exercise the intraerythrocyte potassium concentration returned to base line within 2 min. Exercise did not affect the intraerythrocyte concentrations of sodium and magnesium. The activity of the Na+-K+-ATPase pump and the Na+-K+ cotransport in the erythrocytes during and after exercise was no different from the resting level. The activity of the Na+-Li+ countertransport system on the contrary tended to decrease during exercise. It is concluded that exercise is accompanied by a leakage of potassium out of the erythrocytes without major alterations in the active red cell cationic fluxes.

Increased chemoreceptor output and ventilatory response to sustained hypoxia

1989 ◽  
Vol 67 (3) ◽  
pp. 1157-1163 ◽  
Author(s):  
D. Georgopoulos ◽  
S. Walker ◽  
N. R. Anthonisen
Keyword(s):  
Ventilatory Response ◽  
Minute Ventilation ◽  
Base Line ◽  
Breathing Patterns ◽  
Peripheral Chemoreceptor ◽  
Depressant Action ◽  
Before And After ◽  
End Tidal ◽  
Arterial O2 Saturation ◽  
Sustained Hypoxia

In adult humans the ventilatory response to sustained hypoxia (VRSH) is biphasic, characterized by an initial brisk increase, due to peripheral chemoreceptor (PC) stimulation, followed by a decline attributed to central depressant action of hypoxia. To study the effects of selective stimulation of PC on the ventilatory response pattern to hypoxia, the VRSH was evaluated after pretreatment with almitrine (A), a PC stimulant. Eight subjects were pretreated with A (75 mg po) or placebo (P) on 2 days in a single-blind manner. Two hours after drug administration, they breathed, in succession, room air (10 min), O2 (5 min), room air (5 min), hypoxia [25 min, arterial O2 saturation (SaO2) = 80%], O2 (5 min), and room air (5 min). End-tidal CO2 was kept constant at the normoxic base-line values. Inspiratory minute ventilation (VI) and breathing patterns were measured over the last 2 min of each period and during minutes 3–5 of hypoxia, and nadirs in VI were assessed just before and after O2 exposure. Independent of the day, the VRSH was biphasic. With P and A pretreatment, early hypoxia increased VI 4.6 +/- 1 and 14.2 +/- 1 (SE) l/min, respectively, from values obtained during the preceding room-air period. On A day the hypoxic ventilatory decline was significantly larger than that on P day, and on both days the decline was a constant fraction of the acute hypoxic response.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Ventilatory Response to Hypercapnia as Experimental Model to Study Effects of Oxycodone on Respiratory Depression

2021 ◽  
Vol 16 ◽  
Author(s):  
Lynn R. Webster ◽  
Erik Hansen ◽  
Gregory J. Stoddard ◽  
Austin Rynders ◽  
David Ostler ◽  
...  
Keyword(s):  
Respiratory Depression ◽  
Ventilatory Response ◽  
Volume Flow Rate ◽  
Minute Ventilation ◽  
Statistical Significance ◽  
Adult Males ◽  
Post Dose ◽  
Double Blind ◽  
End Tidal ◽  
End Tidal Co2

Background: Opioid analgesics used to treat pain can cause respiratory depression. However, this effect has not been extensively studied, and life- threatening, opioid-induced respiratory depression remains difficult to predict. We tested the ventilatory response to hypercapnia for evaluating the pharmacodynamic effect of a drug on respiratory depression. Methods: We conducted a randomized, placebo-controlled, double-blind, crossover, study in 12 healthy adult males. Subjects received 2 treatments (placebo and immediate-release oxycodone 30 mg) separated by a 24-hour washout period. Subjects inhaled a mixture of 7% carbon dioxide, 21% oxygen, and 72% nitrogen for 5 minutes to assess respiratory depression. Minute ventilation, respiratory rate, tidal volume, flow rate, end-tidal CO2, and oxygen saturation were recorded continuously at pre-dose and 30, 60, 120, and 180 minutes post-dose. The primary endpoint was the effect on ventilatory response to hypercapnia at 60 minutes post-dose, as assessed by the slope of the linear relationship between minute ventilation and end-tidal CO2. Results: At 60 minutes post-dose, subjects had a mean slope of 2.4 in the oxycodone crossover period, compared to 0.1 in the placebo period (mean difference, 2.3; 95%CI: 0.2 to 4.5; p = 0.035). Statistical significance was likewise achieved at the secondary time points (30, 120, and 180 minutes post-dose, p <0.05). Conclusions: This model for testing ventilatory response to hypercapnia discriminated the effect of 30 mg of oxycodone vs. placebo for up to 3 hours after a single dose. It may serve as a method to predict the relative effect of a drug on respiratory depression.

Ventilatory responses to hypercapnia and hypoxia during continuous aspirin ingestion

1977 ◽  
Vol 43 (6) ◽  
pp. 971-976 ◽  
Author(s):  
D. J. Riley ◽  
B. A. Legawiec ◽  
T. V. Santiago ◽  
N. H. Edelman
Keyword(s):  
Ventilatory Response ◽  
Minute Ventilation ◽  
Normal Subjects ◽  
Carbon Dioxide Tension ◽  
Base Line ◽  
Hypoxic Ventilatory Response ◽  
Ventilatory Responses ◽  
Hypercapnic Ventilatory Response ◽  
The Central Nervous System ◽  
End Tidal

Hypercapnic and hypoxic ventilatory responses were serially measured in nine normal subjects given 3.9 g aspirin (ASA) per day for 9 days. Minute ventilation (VE), end-tidal carbon dioxide tension (PETCO2), venous bicarbonate concentration [HCO3-], oxygen consumption (VO2), hypercapnic ventilatory response (deltaVE/deltaPCO2), and isocapnic hypoxic ventilatory response (A) were determined before, 2 h after the first dose, and at 72-h intervals during the next 14 days. Serum salicylate levels averaged 18.6 +/- 2.0 mg/dl. VE increased (P less than 0.05, PETCO2 decreased (P less than 0.05), and [HCO3-] did not change significantly during drug ingestion. deltaVE/deltaPCO2 increased gradually to a value 37% greater than control by day 3 and remained constant (P less 0.01). A increased by 251% and VO2 by 18% within 2 h and remained constant for the remainder of the ASA period (P less than 0.01). All values returned to base line within 24 h following cessation of ASA. We conclude that during continuous ASA ingestion there is a gradual increase of hypercapnic ventilatory response. This may reflect slow entrance of ASA into the central nervous system. In contrast, there is a rapid rise in hypoxic ventilatory response which may be mechanically linked to changes in metabolic rate.

Comparative physiological study of arbutamine with exercise in humans

2000 ◽  
Vol 98 (4) ◽  
pp. 489-494 ◽  
Author(s):  
Sharon L. LOVELL ◽  
Suzanne M. MAGUIRE ◽  
Frances TURTLE ◽  
Garry McDOWELL ◽  
Norman P. S. CAMPBELL ◽  
...  
Keyword(s):  
Minute Ventilation ◽  
Volume Ratio ◽  
Serum Lactate ◽  
Gas Analysis ◽  
Pharmacological Stress ◽  
Direct Stimulation ◽  
Oxygen Pulse ◽  
Pharmacological Stress Testing ◽  
Artery Disease ◽  
End Tidal

Pharmacological stress testing may be used in the diagnosis of coronary artery disease when there are contra-indications to the use of conventional exercise protocols.The responses to such testing using arbutamine and to conventional treadmill exercise were compared in eight patients. Respiratory gas analysis and cardiovascular observations were performed during both tests. For an equivalent increment in heart rate, both protocols increased systolic blood pressure and serum lactate. Minute ventilation and oxygen consumption also rose during both protocols, but much more so with exercise. The end-tidal partial pressure of CO2 [35.1 (S.D. 3.1) to 30.8 (6.6) mmHg] and the dead space/tidal volume ratio (VD/VT) [0.37 (0.09) to 0.33 (0.08)] fell significantly during arbutamine infusion, but the respiratory exchange ratio did not change during either protocol. Oxygen pulse, a marker of stroke volume, did not change significantly after arbutamine, but rose markedly after exercise [arbutamine, 3.9 (1.1) to 3.37 (0.7) ml·min-1·beat-1; exercise, 4.7 (1.4) to 16.1 (4.6) ml·min-1·beat-1 (P < 0.0001 compared with baseline); difference between peak responses: P < 0.0001]. We conclude that arbutamine simulates some of the physiological responses to exercise, although a number of these responses are less marked than during conventional exercise, in particular cardiac output (oxygen pulse). An increase in ventilation is produced, possibly due to direct stimulation of arterial chemoreceptors. These data suggest that the main action of arbutamine is to increase central drive rather than to establish peripheral demand.

Effect of naloxone on perceived exertion and exercise capacity during maximal cycle ergometry

2002 ◽  
Vol 93 (6) ◽  
pp. 2023-2028 ◽  
Author(s):  
Anthony L. Sgherza ◽  
Kenneth Axen ◽  
Randi Fain ◽  
Robert S. Hoffman ◽  
Christopher C. Dunbar ◽  
...  
Keyword(s):  
Exercise Capacity ◽  
Perceived Exertion ◽  
Minute Ventilation ◽  
Work Capacity ◽  
Cycle Ergometer ◽  
Endogenous Opioids ◽  
Opioid Antagonist ◽  
Double Blind ◽  
Cycle Ergometer Test ◽  
Physiological Limits

We assessed the effects of naloxone, an opioid antagonist, on exercise capacity in 13 men and 5 women (mean age = 30.1 yr, range = 21–35 yr) during a 25 W/min incremental cycle ergometer test to exhaustion on different days during familiarization trial and then after 30 mg (iv bolus) of naloxone or placebo (Pl) in a double-blind, crossover design. Minute ventilation (V˙e), O2 consumption (V˙o 2), CO2 production, and heart rate (HR) were monitored. Perceived exertion rating (0-10 scale) and venous samples for lactate were obtained each minute. Lactate and ventilatory thresholds were derived from lactate and gas-exchange data. Blood pressure was obtained before exercise, 5 min postinfusion, at maximum exercise, and 5 min postexercise. There were no control-Pl differences. The naloxone trial demonstrated decreased exercise time (96% Pl; P < 0.01), total cumulative work (96% Pl; P < 0.002), peakV˙o 2 (94% Pl; P < 0.02), and HR (96% Pl; P < 0.01). Other variables were unchanged. HR and V˙e were the same at the final common workload, but perceived exertion was higher (8.1 ± 0.5 vs. 7.1 ± 0.5) after naloxone than Pl ( P < 0.01). The threshold for effort perception amplification occurred at ∼60 ± 4% of Pl peakV˙o 2. Thus we conclude that peak work capacity was limited by perceived exertion, which can be attenuated by endogenous opioids rather than by physiological limits.

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