PURPOSE: Examine the effects of chronic metabolic acidosis on ventilatory, respiratory mechanical and perceptual responses to strenuous exercise.
METHODS: In a randomized, single-blind, placebo-controlled, cross-over study, 12 healthy (31±3 yrs, mean±SEM; 3 men) volunteers performed symptom-limited incremental cycle exercise tests after ingesting 0.2 g of ammonium chloride (NH4Cl)/kg/day or 0.025 g sodium chloride (NaCl)/kg/day for 3 days.
RESULTS: Compared with NaCl, NH4Cl induced a partially-compensated metabolic acidosis: arterialized capillary [H+] increased by 12.5±2.0 nEq/L, while arterialized capillary PCO2 and the plasma [strong ion difference] decreased by 8.0±1.7 mmHg and 9.1±1.2 mEq/L, respectively (all p<0.001). Exercise performance was significantly reduced after treatment with NH4Cl vs. NaCl: peak V'O2, peak cycle work rate and the duration of loaded pedaling decreased by 10%, 14% and 13%, respectively (all p<0.01). Compared with NaCl, NH4Cl increased the ventilatory response to exercise: ventilation (V'E), tidal volume (VT) and the V'E/V'CO2 ratio increased by ~20%, 11% and 26%, respectively, with attendant reductions in end-tidal PCO2 (by ~25%) at a standardized submaximal work rate (iso-work) of 146 watts (all p<0.01). The magnitude of the increased V'E/V'CO2 at iso-work correlated with concurrent changes in [H+] at rest (r2=0.746,p<0.001). Breathlessness intensity ratings were significantly higher during exercise after treatment with NH4Cl vs. NaCl (by 1.1±0.3 Borg units at iso-work, p<0.01); however, breathlessness-V'E relationships were relatively preserved throughout much of exercise in NH4Cl vs. NaCl. Dynamic mechanical constraints on VT expansion with attendant increases in breathlessness intensity were observed near the limits of tolerance after treatment with NH4Cl vs. NaCl.
CONCLUSION: (1) NH4Cl-induced increases in exertional breathlessness reflected the awareness of increased V'E, secondary to alterations in the regulated level of [H+]; and (2) dynamic respiratory mechanical constraints contributed to breathlessness near end-exercise after treatment with NH4Cl.
CLINICAL IMPLICATIONS: The novel results of this study may help to explain the mechanism(s) of increased activity-related breathlessness in patients with acute or chronic acid-base disturbances.
DISCLOSURE: Dennis Jensen, No Financial Disclosure Information; No Product/Research Disclosure Information