Disturbance of CO₂ Elimination in the Lungs by Carbonic Anhydrase Inhibition

Abstract

Carbonic anhydrase in the red blood cell and in the pulmonary endothelium facilitates the elimination of CO₂ in the lungs. Although a carbonic anhydrase inhibitor, such as acetazolamide which is frequently used in patients with glaucoma or with metabolic alkalosis, is known to impair the CO₂ elimination in the lungs, the dose-response curve of CO₂ elimination with acetazolamide has not been well documented in CO₂ homeostasis. In the present study, the effects of inhibited carbonic anhydrase were tested in 8 anesthetized dogs; various dosages of acetazolamide were used. When the administered clinical dosage of acetazolamide increased from 5 to 20mg/kg, Pa_CO2, Pv_CO2, arterial-alveolar P_CO2 difference (a-AD_CO2), and physiological VD/VT ratio increased progressively to 52.0±2.1Torr, 58.0±3.0Torr, 23.4±1.2Torr, and by 19.2±1.8% (S.E.) respectively, whereas inhibition rate of red blood cell carbonic anhydrase (RCA) activity increased progressively to 73.1±2.1% (S.E.). On the other hand, PA_CO2 decreased to 27.1±1.8Torr (S.E.) upon the first injection of 5mg/kg of acetazolamide, but PA_CO2 did not change further upon 3 additional 5mg/kg injections. Mixed venous-arterial P_CO2 difference ((v-a)P_CO2), V_CO2, and anatomical VD/VT ratio were unchanged by the administration of any doses of acetazolamide.