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

Abstract
The relationships of changes in respiration and brain blood flow index to alterations in arterial and internal jugular venous blood pCO2, [HCO3-], 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 CO2 breathing. Intravenous infusion of NaHCO3 solution (ca. 2.4 mEq/kg) while maintaining alveolar pCO2 at 50 mm Hg revealed the responses to a lowering of blood [H+] without concurrent change in arterial or internal jugular venous pCO2. Brain blood flow index varied directly with alteration in blood pCO2 and was unaffected by changes in blood pH not produced by pCO2 change. Respiratory measurements indicated a prominent relationship between respiration and blood hydrogen ion concentration, the reversal of the acidemia normally associated with CO2 administration removing approximately 45% of respiratory stimulation induced by hypercapnia. The remaining 55% of the increased ventilation caused by CO2 breathing was not directly related to changes in arterial or internal jugular venous blood pH or [HCO3-]. The residual respiratory effect of CO2 administration was correlated, not only with alteration of pCO2, but with calculated changes in the pH of cerebrospinal fluid. Thus, the total respiratory stimulation produced by CO2 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 pCO2. 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 pCO2, comparable stimulant effects of molecular CO2 cannot be demonstrated without somewhere producing concurrent modification of pH. Submitted on August 22, 1960