During hypercapnic acidosis induced by ‘apneic oxygenation,’ one observes in the dog a rise in plasma catecholamine levels in the presence of a constant oxygen uptake (Qo2) and a rise in mean blood pressure. When pH is maintained constant or alkaline by infusion of T.H.A.M. (2 amino 2 hydroxymethyl 1–3 propane diol), Qo2 remains constant while plasma catecholamines and blood pressure do not change although total plasma CO2 shows a twofold increase. When blood pH is rapidly shifted from 6.99 ± .03 to 7.52 ± .02, Qo2 increased by 39%, while plasma catecholamine levels were rapidly re-established to normal. The infusion of 1 µg/kg/min. of epinephrine, norepinephrine or isoproterenol will also produce a significant increase in Qo2 and blood pressure in the apneic dog when arterial blood pH is maintained normal or alkaline; but the same dose of epinephrine fails to change significantly Qo2 or blood pressure when arterial blood pH is maintained between 6.97 and 7.28.

Thirteen dogs were paralyzed with succinylcholine and ventilated at constant rate and volume with 100% O2. The control animals were given an i.v. infusion of .15–.30 m lactic acid at the rate of .33 mm/kg/min. for the first 30 minutes and at the rate of .16 mm/kg/min. for the following 30 minutes. After 1 hour pH had fallen from 7.39 to 7.00, diuresis was maintained and mean blood pressure, catecholamine and glucose blood levels were unchanged. By contrast animals with a similar fall in pH produced by CO2 retention presented signs of marked stimulation of the sympatho-adrenal system, such as increased blood pressure, anuria, elevated catecholamine and glucose blood levels. These data indicate the importance of intracellular [H+] changes in the regulation of circulation. The fixed ‘addition acidosis’ produced by lactic acid infusion as described, was corrected by an i.v. infusion of .33 mm/kg/min. of .33 m tris(hydroxymethyl) aminomethane (THAM) which was administered during the second 30-minute period of lactic acid infusion. A similarly produced acidosis required for correction an amount of bicarbonate of sodium double that of THAM.

Eight dogs maintained in ‘apneic oxygenation’ for 60 minutes were given a .3 M intravenous infusion of 2-amino-2-(hydroxymethyl)-1, 3-propanediol (THAM) in a .3% NaCl solution at the rate of 1.1 ml/ kg/min. After 1 hour of apnea, arterial O2 saturation was 100%, plasma CO2 53.2 mm/l., plasma HCO–3 50.6 mm/l., arterial blood pH 7.37 and PaCO2 98 mm Hg. Blood pressure remained close to the preapneic control period and intracranial pressure did not change significantly. Plasma catecholamines levels did not change. There was a fall in hematocrit, in Na+ and Cl– plasma concentration while K+ did not change. After a 20-minute lag, urine output equaled fluid input. Urinary pH was 7.54, HCO–3 concentration 89 mm/l., THAM 85 mm/l. and 18–28% of the total CO2 produced by the animal during apnea was recovered in the urine excreted during that time. All the animals survived, indicating that the dog will tolerate well a plasma concentration of CO2 over twice its normal level when its two fractions HCO–3 and H2CO3 are in suitable proportion to maintain the biological neutrality of the internal environment (e.g. 7.40). In the presence of a normal pH and an elevated pCO2 there is no measurable stimulation of the sympathoadrenal system and the circulation is not altered.