The effects of carbonic anhydrase inhibitors on exercise performance in acute hypoxia

Abstract

Acute mountain sickness (AMS) can occur due to rapid altitude ascents and/or insufficient acclimatization. Acetazolamide (AZ) is commonly prescribed for AMS prophylaxis but appears to inhibit exercise performance. Methazolamide (MZ) has similar prophylactic benefits but does not have a similar decrement in isolated small muscle mass exercise in normoxia. We compared whole-body exercise performance in acute hypoxia (FIO2 = 0.15) between AZ and MZ and hypothesized that time trial duration will be the shortest in MZ compared with AZ and placebo (PLA). Fifteen young healthy participants completed 5 testing visits: day 1 maximal exercise test, day 2 a familiarization visit, and Day 3-5 were the experimental visits. Each experimental visit involved a 5-km hypoxic cycling time trial performed after a 2-day dosing protocol of either AZ (250mg t.i.d.), MZ (100mg b.i.d.) or PL (t.i.d.); the order was randomized and double-blinded. Before and after each experimental time trial, capillary blood samples were taken, and maximal voluntary contractions of the quadriceps were performed. AZ and MZ resulted in a partially compensated metabolic acidosis at rest (capillary H+ 47±3, 43±2, 39±2 nmol for AZ, MZ and PLA respectively, p<0.01). Time to complete 5-km on PLA (562±32s, p<0.01) was significantly faster than AZ and MZ (577±38 vs. 581±37s respectively), with no differences between AZ and MZ (p=0.96). The 5-km average ventilatory efficiency (V̇E/V̇CO2) listed from greatest to least was MZ, AZ and PLA (46±6, 43±4, 37±3 respectively) and were all significantly different (p<0.05). There were no differences in the average ventilation (124±27, 127±24, 127±19 L/min respectively) and oxyhemoglobin saturation (87±2, 88±2, 88±3 respectively) between PLA, AZ and MZ (p>0.05). Peak quadricep torque before exercise was found to be significantly lower in AZ compared to PLA and MZ (543± 77, 574± 76, 552± 67 N respectively, p<0.05). In conclusion, both AZ and MZ impaired whole-body exercise performance in acute hypoxia and this finding might be important to consider for high altitude occupations.