H⁺ and pCO₂ as chemical factors in respiratory and cerebral circulatory control

The relationships of changes in respiration and brain blood flow index to alterations in arterial and internal jugular venous blood pCO 2 , [HCO 3 - ], and pH were studied in normal men. Observations during control of alveolar pCO2, first at 44 and then at 50 mm Hg, represented the effects of CO 2 breathing. Intravenous infusion of NaHCO 3 solution (ca. 2.4 mEq/kg) while maintaining alveolar pCO 2 at 50 mm Hg revealed the responses to a lowering of blood [H+] without concurrent change in arterial or internal jugular venous pCO 2 . Brain blood flow index varied directly with alteration in blood pCO 2 and was unaffected by changes in blood pH not produced by pCO 2 change. Respiratory measurements indicated a prominent relationship between respiration and blood hydrogen ion concentration, the reversal of the acidemia normally associated with CO 2 administration removing approximately 45% of respiratory stimulation induced by hypercapnia. The remaining 55% of the increased ventilation caused by CO 2 breathing was not directly related to changes in arterial or internal jugular venous blood pH or [HCO 3 - ]. The residual respiratory effect of CO 2 administration was correlated, not only with alteration of pCO 2 , but with calculated changes in the pH of cerebrospinal fluid. Thus, the total respiratory stimulation produced by CO 2 breathing, and its diminution by bicarbonate infusion, can be quantitatively described either in terms of a single stimulus index, hydrogen ion concentration, or in terms of two factors, pH and pCO 2 . Choice between single and multiple acid-base factors as indices of chemical stimuli in respiratory control remains arbitrary. However, the discussion re-emphasizes that, while respiratory changes do occur when blood pH is altered without change of blood or central pCO 2 , comparable stimulant effects of molecular CO 2 cannot be demonstrated without somewhere producing concurrent modification of pH. Submitted on August 22, 1960