Impact of NaHCO3- on Exercise Hyperpnea
Condition: Pulmonary Ventilation
Study type: Interventional
Phase: Early Phase 1

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Sodium Bicarbonate; Sodium Chloride
Intervention type(s): Drug; Drug
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Exercise; Sodium Bicarbonate; Ventilatory equivalent for carbon dioxide