Kinetics of CO2 excretion and intravascular pH disequilibria during carbonic anhydrase inhibition

Abstract

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.