Pulmonary Ventilation Clinical Trial
Official title:
Effect of Induced Metabolic Alkalosis by Sodium Bicarbonate Administration on the Ventilatory Response to Exercise in Healthy Adults
An abnormally high V̇E/V̇CO2 response to exercise is a key pathophysiological feature of patients with chronic cardiopulmonary disease that is associated with adverse health outcomes. It follows that any intervention capable of decreasing the V̇E/V̇CO2 response to exercise has the potential to improve clinical and/or patient-reported outcomes. The investigators of this trial will compare the effects of orally administered sodium chloride (4 g, placebo) and sodium bicarbonate (0.3 g/kg of body mass) on ventilation, breathing pattern, dynamic operating lung volume, gas exhange, cardiovascular, metabolic and symptom parameters during symptom-limited, high-intensity, constant-work-rate cycle exercise testing in healthy adults aged 20-40 years.
The ventilatory response (V̇E) to exercise-induced increases in the rate of CO2 production
(V̇CO2) depends on the regulated level of arterial PCO2 (PaCO2) and the dead space to tidal
volume ratio (VD/VT).
An abnormally high V̇E/V̇CO2 response to exercise, reflecting a high VD/VT and/or low PaCO2
equilibrium point, is a key pathophysiological feature of patients with chronic
cardiopulmonary disease, including heart failure, pulmonary arterial hypertension,
interstitial lung disease and chronic obstructive pulmonary disease. In these patient
groups, exercise ventilatory inefficiency is associated with: disease severity and
progression; exercise intolerance; exertional breathlessness; and increased risk of
hospitalization, major cardiac events and mortality. It follows that any intervention
capable of decreasing the V̇E/V̇CO2 response to exercise has the potential to improve
clinical and/or patient-reported outcomes. Unfortunately, our ability to enhance exercise
ventilatory efficiency is limited by the fact that, with the possible exception of lung
volume reduction surgery in chronic obstructive pulmonary disease and pulmonary vasodilator
therapy in pulmonary arterial hypertension and heart failure, ventilation-perfusion
abnormalities reflecting a high VD/VT are often irreversible.
A largely unexplored approach to decreasing the V̇E/V̇CO2 response to exercise is increasing
the PaCO2 equilibrium point by inducing a metabolic alkalosis via administration of an
alkalizing agent such as sodium bicarbonate (NaHCO3). Thus, the primary objective of this
randomized, double blind, placebo controlled, crossover study was to test the hypothesis
that increasing the PaCO2 equilibrium point via induced acute metabolic alkalosis by
single-dose oral administration of NaHCO3 would decrease in the V̇E/V̇CO2 ratio at its
lowest point ("nadir") during high-intensity constant-load cycle exercise testing in healthy
adults.
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