TY - JOUR
T1 - Methazolamide Plus Aminophylline Abrogates Hypoxia-Mediated Endurance Exercise Impairment
AU - Scalzo, Rebecca L.
AU - Binns, Scott E.
AU - Klochak, Anna L.
AU - Giordano, Gregory R.
AU - Paris, Hunter L.R.
AU - Sevits, Kyle J.
AU - Beals, Joseph W.
AU - Biela, Laurie M.
AU - Larson, Dennis G.
AU - Luckasen, Gary J.
AU - Irwin, David
AU - Schroeder, Thies
AU - Hamilton, Karyn L.
AU - Bell, Christopher
N1 - Publisher Copyright:
© 2015 Mary Ann Liebert, Inc.
PY - 2015/12
Y1 - 2015/12
N2 - Scalzo, Rebecca L., Scott E. Binns, Anna L. Klochak, Gregory R. Giordano, Hunter L.R. Paris, Kyle J. Sevits, Joseph W. Beals, Laurie M. Biela, Dennis G. Larson, Gary J. Luckasen, David Irwin, Thies Schroeder, Karyn L. Hamilton, and Christopher Bell. Methazolamide plus aminophylline abrogates hypoxia-mediated endurance exercise impairment. High Alt Med Biol 16:331-342, 2015.-In hypoxia, endurance exercise performance is diminished; pharmacotherapy may abrogate this performance deficit. Based on positive outcomes in preclinical trials, we hypothesized that oral administration of methazolamide, a carbonic anhydrase inhibitor, aminophylline, a nonselective adenosine receptor antagonist and phosphodiesterase inhibitor, and/or methazolamide combined with aminophylline would attenuate hypoxia-mediated decrements in endurance exercise performance in humans. Fifteen healthy males (26 ± 5 years, body-mass index: 24.9 ± 1.6 kg/m2; mean ± SD) were randomly assigned to one of four treatments: placebo (n = 9), methazolamide (250 mg; n = 10), aminophylline (400 mg; n = 9), or methazolamide (250 mg) with aminophylline (400 mg; n = 8). On two separate occasions, the first in normoxia (FIO2 = 0.21) and the second in hypoxia (FIO2 = 0.15), participants sat for 4.5 hours before completing a standardized exercise bout (30 minutes, stationary cycling, 100 W), followed by a 12.5-km time trial. The magnitude of time trial performance decrement in hypoxia versus normoxia did not differ between placebo (+3.0 ± 2.7 minutes), methazolamide (+1.4 ± 1.7 minutes), and aminophylline (+1.8 ± 1.2 minutes), all with p > 0.09; however, the performance decrement in hypoxia versus normoxia with methazolamide combined with aminophylline was less than placebo (+0.6 ± 1.5 minutes; p = 0.01). This improvement may have been partially mediated by increased SpO2 in hypoxia with methazolamide combined with aminophylline compared with placebo (73% ± 3% vs. 79% ± 6%; p < 0.02). In conclusion, coadministration of methazolamide and aminophylline may promote endurance exercise performance during a sojourn at high altitude.
AB - Scalzo, Rebecca L., Scott E. Binns, Anna L. Klochak, Gregory R. Giordano, Hunter L.R. Paris, Kyle J. Sevits, Joseph W. Beals, Laurie M. Biela, Dennis G. Larson, Gary J. Luckasen, David Irwin, Thies Schroeder, Karyn L. Hamilton, and Christopher Bell. Methazolamide plus aminophylline abrogates hypoxia-mediated endurance exercise impairment. High Alt Med Biol 16:331-342, 2015.-In hypoxia, endurance exercise performance is diminished; pharmacotherapy may abrogate this performance deficit. Based on positive outcomes in preclinical trials, we hypothesized that oral administration of methazolamide, a carbonic anhydrase inhibitor, aminophylline, a nonselective adenosine receptor antagonist and phosphodiesterase inhibitor, and/or methazolamide combined with aminophylline would attenuate hypoxia-mediated decrements in endurance exercise performance in humans. Fifteen healthy males (26 ± 5 years, body-mass index: 24.9 ± 1.6 kg/m2; mean ± SD) were randomly assigned to one of four treatments: placebo (n = 9), methazolamide (250 mg; n = 10), aminophylline (400 mg; n = 9), or methazolamide (250 mg) with aminophylline (400 mg; n = 8). On two separate occasions, the first in normoxia (FIO2 = 0.21) and the second in hypoxia (FIO2 = 0.15), participants sat for 4.5 hours before completing a standardized exercise bout (30 minutes, stationary cycling, 100 W), followed by a 12.5-km time trial. The magnitude of time trial performance decrement in hypoxia versus normoxia did not differ between placebo (+3.0 ± 2.7 minutes), methazolamide (+1.4 ± 1.7 minutes), and aminophylline (+1.8 ± 1.2 minutes), all with p > 0.09; however, the performance decrement in hypoxia versus normoxia with methazolamide combined with aminophylline was less than placebo (+0.6 ± 1.5 minutes; p = 0.01). This improvement may have been partially mediated by increased SpO2 in hypoxia with methazolamide combined with aminophylline compared with placebo (73% ± 3% vs. 79% ± 6%; p < 0.02). In conclusion, coadministration of methazolamide and aminophylline may promote endurance exercise performance during a sojourn at high altitude.
KW - high-altitude
KW - methazolamide
KW - theophylline
UR - http://www.scopus.com/inward/record.url?scp=84951973453&partnerID=8YFLogxK
U2 - 10.1089/ham.2015.0066
DO - 10.1089/ham.2015.0066
M3 - Article
C2 - 26680684
AN - SCOPUS:84951973453
SN - 1527-0297
VL - 16
SP - 331
EP - 342
JO - High Altitude Medicine and Biology
JF - High Altitude Medicine and Biology
IS - 4
ER -