Carbon dioxide and the HCO 3 ion as specific respiratory stimulants

It has been noted by Howell, Collip, Dale and Evans, the author and others that the intravenous injection of sodium bicarbonate may act as either a respiratory or circulatory stimulant, eliciting hypernea or a marked rise in the blood pressure. Such injection obviously increases the hydrogen ion concentration of the blood and inasmuch as it produces a slight dilution, it decreases the amount of carbon dioxide in the blood eliciting the stimulation. The increased respiration is, therefore contrary to the usually accepted laws of respiration. The only apparent change in the blood which might elicit stimulation is the greatly increased number of HCO₃ ions. Collip, therefore, suggests that the HCO₃ ion exerts a specific stimulating action on the respiratory center.

We believe, however, that this anomalous result may be otherwise explained. When the carbon dioxide is dissolved in water it exists primarily in three forms—dissolved CO₂ molecules, dissolved undissociated H₂CO₃—molecules and dissociated H₂CO₃—thus . Addition of sodium bicarbonate to the solution pushes the reaction to the left increasing both the dissolved CO₂ and the undissociated H₂CO₃. If we accept the view that the dissolved CO₂, and the undissociated H₂CO₃, diffuse freely into cells while the ions as such do not penetrate to any appreciable extent it is apparent that the injection of sodium bicarbonate increases the freely diffusable forms of carbon dioxide at the expense of the poorly diffusible ions and in that way increases the acid effects of the blood, at least on the interior of the cells (and possibly in the lymph bathing the cells as will be discussed in a later paper) even though the actual sum total of the original dissolved carbon dioxide in its various forms is not increased and the hydrogen ion concentrate of the blood is actually decreased.