QUANTITATIVE-ANALYSIS OF CO2 TRANSPORT AT REST AND DURING MAXIMAL EXERCISE

Exercise to exhaustion in rats and man was studied befor and after administration of acetazolamide. In rats the dose (100 mg/kg) completely inhibited red cell carbonic anhydrase. In man a clinical dose (10 mg/kg) was used, and the degree of inhibition of HCO3- dehydration by red cell isoenzymes B and C was measured. These results and relevant data from the literature were used to describe in model form the contributions to pulmonary CO2 output of the carbonic anhydrase catalyzed reaction HCO3- → CO2, the uncatalyzed reaction, carbamino hemoglobin, and dissolved CO2 during rest and exercise. Conclusions are: (1) at rest, 78% of CO2 exchange in the lung is mediated by carbonic anhydrase catalyzed dehydration of HCO3-; at exercise this rises to 90%; (2) when carbonic anhydrase is totally at rest large PCO gradients are set up in tissue and lung, increasing the uncatalyzed rate and dissolved CO2 participation, so that CO2 is evolved at normal rate without enzyme (rat, dog and man); (3) during exercise with complete inhibition (rat), similar or larger gradients are created; nevertheless, exercise tolerance was impaired; (4) in maximal exercise (man), the clinical dose and resulting unbound plasma concentrations of acetazolamide (7.5 μM) yield enzyme inhibition of 98.8%. New gradients of CO2 are established, which together with increased cardiac output and the residual enzyme, can effect CO2 evolution 15 times the normal resting value; and (5) the data suggest that in the complete absence of carbonic anhydrase, CO2 evolution would not proceed at an adequate rate in maximal exercise. In general, this analysis shows that carbonic anhydrase makes carriage and evolution of CO2 possible across small gradients. The large amount of enzyme serves to keep these gradients narrow; the reserve or 'excess' enzyme (above the required for no perturbation in ventilation or blood-gas chemistry) is a 17-fold at rest and 6-fold in excercise. When enzyme is diminished or absent, gradients increase to the in point of physiological effectiveness, except (probably) in the most severe exercise. The increased gradients produced effects such as increased cerebral blood flow, unusual taste for CO2 and certain clinical signs and symptoms, but the new respiratory steady-state permits quantitative evolution of CO2. © 1978.