Relationships Between Ventilatory and Heart Rate Responses to Hypobaric Hypoxia: Influences of Acetazolamide

Acetazolamide (AZ) is often used for prevention and/or treatment of acute mountain sickness (AMS), particularly during rapid ascent to altitudes > 3000 m. Although it is known that AZ augments ventilation (VE), it is unclear how this may affect chemoreflex relationships among ventilatory variables and control of heart rate (HR). PURPOSE: The purpose of the study was two-fold: 1), establish the effect of AZ and hypobaric hypoxia (HH) on VE and HR; and 2), estimate the effect of AZ on the chemoreflex relationship between VE and HR. METHODS: After completing familiarization testing at sea level (SL), 10 male volunteers (22 ± 3 yr; height: 176.0 ± 7.1 cm; weight: 77.5 ± 11.5 kg) completed two 30 hr HH exposures (~ 3500 m); one while taking AZ (500 mg/day) and one while taking a placebo, in a single-blind crossover design in random order. Ventilation and gas exchange, including HR, VE, and end-tidal partial pressure of carbon dioxide (PetCO2), were measured three times at rest, once at SL and then at ~2 and 24 hours into exposure to simulated altitude. A linear mixed model with a random intercept per subject was utilized to evaluate the influences of AZ and HH on HR, VE, and PetCO2. RESULTS: VE increased and PetCO2 decreased (p<0.05 for all) with both HH and AZ. HR increased with HH (p<0.001), but there was no further effect of AZ (p=0.15). HR was related to both VE (p=0.009) and PetCO2 (p<0.001) in all subjects. AZ shifted the relationships between HR, VE, and PetCO2, but there was no interaction between AZ and HH (p>0.10 for both). Overall, while AZ augmented VE it did not affect the slope of the relationship between HR and VE, but rather shifted the relationship to lower VE values. CONCLUSION: During exposure to HH, activation of the chemoreflex augments both ventilation and sympathetic outflow to the heart causing increased HR. Our present findings that VE tended to be lower for a given level of HR during AZ trials, suggest that AZ may have an influence to shift the relationship between these two chemoreflex-mediated events. Funded by USAMRMC; author views not official US Army or DOD policy.