PURPOSE: The neurophysiology of breathlessness is only partially understood, but the awareness of increased brainstem respiratory motor drive is likely contributory. Accordingly, we examined the effects of metabolic acidosis on the intensity and unpleasantness of perceived breathlessness during increased chemostimulation in healthy humans.
METHODS: In a randomized, single-blind, placebo-controlled, cross-over study, 12 healthy (31±3 yrs, mean±SEM; 3 men) volunteers performed symptom-limited hyperoxic CO2 rebreathing 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 and significantly increased central chemoreflex responsiveness, as evidenced by a reduced threshold and increased sensitivity of the ventilatory response to progressive hypercapnia (both p<0.05). The duration of rebreathing decreased by ~35% after treatment with NH4Cl vs. NaCl, despite end-tidal PCO2 (PETCO2) being ~9.5 mmHg lower at the point of symptom-limitation in the former (both p<0.001). The intensity and unpleasantness of breathlessness were not significantly (p>0.05) different between-treatments at a standardized ventilation (V'E) of ~60 L/min during rebreathing. In contrast, both the intensity and unpleasantness of breathlessness were significantly greater (by 2.5 and 3.2 Borg units, respectively; both p<0.01) at a standardized hypercapnic PETCO2 of ~55 mmHg during rebreathing after treatment with NH4Cl vs. NaCl. These changes were accompanied by an 18 L/min increase in V'E (p=0.009).
CONCLUSION: NH4Cl-induced increases in the intensity and unpleasantness of perceived breathlessness for a given PETCO2 during rebreathing reflected the awareness of increased V'E, which accompanied the decreased threshold and increased sensitivity of the central respiratory chemoreflex control system.
CLINICAL IMPLICATIONS: These novel findings may help to explain the effects of chronic acid-base disturbances on ventilatory control and respiratory sensation in patients with respiratory and/or metabolic abnormalities.
DISCLOSURE: Dennis Jensen, No Financial Disclosure Information; No Product/Research Disclosure Information