Cardenas, Victor, Jr., Thomas A. Heming, and Akhil Bidani.Kinetics of CO2 excretion and intravascular pH disequilibria during carbonic anhydrase inhibition. J. Appl. Physiol. 84(2): 683–694, 1998.—Inhibition of carbonic anhydrase (CA) activity (activity in red blood cells and activity available on capillary endothelium) results in decrements in CO2 excretion (V˙co 2) and plasma-erythrocyte CO2-[Formula: see text]-H+disequilibrium as blood travels around the circulation. To investigate the kinetics of changes in blood [Formula: see text]and pH during progressive CA inhibition, we used our previously detailed mathematical model of capillary gas exchange to analyze experimental data of V˙co 2and blood-gas/pH parameters obtained from anesthetized, paralyzed, and mechanically ventilated dogs after treatment with acetazolamide (Actz, 0–100 mg/kg iv). Arterial and mixed venous blood samples were collected via indwelling femoral and pulmonary arterial catheters, respectively. Cardiac output was measured by thermodilution. End-tidal[Formula: see text], as a measure of alveolar[Formula: see text], was obtained from continuous records of airway [Formula: see text] above the carina. Experimental results were analyzed with the aid of a mathematical model of lung and tissue-gas exchange. Progressive CA inhibition was associated with stepwise increments in the equilibrated mixed venous-alveolar [Formula: see text] gradient (9, 19, and 26 Torr at 5, 20, and 100 mg/kg Actz, respectively). The maximum decrements in V˙co 2were 10, 24, and 26% with 5, 20, and 100 mg/kg Actz, respectively, without full recovery ofV˙co 2 at 1 h postinfusion. Equilibrated arterial [Formula: see text]overestimated alveolar [Formula: see text], and tissue [Formula: see text] was underestimated by the measured equilibrated mixed venous blood[Formula: see text]. Mathematical model computations predicted hysteresis loops of the instantaneous CO2-[Formula: see text]-H+relationship and in vivo blood[Formula: see text]-pH relationship due to the finite reaction times for CO2-[Formula: see text]-H+reactions. The shape of the hysteresis loops was affected by the extent of Actz inhibition of CA in red blood cells and plasma.