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

Victor Cardenas, Thomas A. Heming, Akhil Bidani

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31 Scopus citations


Inhibition of carbonic anhydrase (CA) activity (activity in red blood cells and activity available on capillary endothelium) results in decrements in CO2 excretion (V̇CO2) and plasma-erythrocyte CO2-HCO3/-H+ disequilibrium as blood travels around the circulation. To investigate the kinetics of changes in blood PCO2 and pH during progressive CA inhibition, we used our previously detailed mathematical model of capillary gas exchange to analyze experimental data of V̇CO2 and 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 PCO2, as a measure of alveolar PCO2, was obtained from continuous records of airway PCO2 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 PCO2 gradient (9, 19, and 26 Torr at 5, 20, and 100 mg/kg Actz, respectively). The maximum decrements in V̇CO2 were 10, 24, and 26% with 5, 20, and 100 mg/kg Actz, respectively, without full recovery of V̇CO2 at 1 h postinfusion. Equilibrated arterial PCO2 overestimated alveolar PCO2, and tissue PCO2 was underestimated by the measured equilibrated mixed venous blood PCO2. Mathematical model computations predicted hysteresis loops of the instantaneous CO2-HCO3/-H+ relationship and in vivo blood PCO2-pH relationship due to the finite reaction times for CO2-HCO3/-H+ reactions. The shape of the hysteresis loops was affected by the extent of Actz inhibition of CA in red blood cells and plasma.

Original languageEnglish (US)
Pages (from-to)683-694
Number of pages12
JournalJournal of Applied Physiology
Issue number2
StatePublished - Feb 1998


  • Acetazolamide
  • Carbonic anhydrase
  • Gas exchange

ASJC Scopus subject areas

  • General Medicine


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