Effects of chronic acetazolamide administration on gas exchange and acid-base control in pulmonary circulation in exercising horses

Abstract

Reasons for performing study: Carbonic anhydrase (CA) catalyses the hydration/dehydration reaction of CO2 and increases the rate of Cl- and HCO3- exchange between the erythrocytes and plasma. Therefore, chronic inhibition of CA has a potential to attenuate CO2 output and induce greater metabolic and respiratory acidosis in exercising horses.Objectives: To determine the effects of Carbonic anhydrase inhibition on CO2 output and ionic exchange between erythrocytes and plasma and their influence on acid-base balance in the pulmonary circulation (across the lung) in exercising horses with and without CA inhibition. Methods: Six horses were exercised to exhaustion on a treadmill without (Con) and with CA inhibition (AczTr). CA inhibition was achieved with administration of acetazolamide (10 mg/kg bwt t.i.d. for 3 days and 30 mg/kg bwt before exercise). Arterial, mixed venous blood and CO2 output were sampled at rest and during exercise. An integrated physicochemical systems approach was used to describe acid base changes. Results: AczTr decreased the duration of exercise by 45% (P<0.0001). During the transition from rest to exercise CO2 output was lower in AczTr (P<0.0001). Arterial PCO2 (P<0.0001; mean ± s.e. 71 ± 2 mmHg AczTr, 46 ± 2 mmHg Con) was higher, whereas hydrogen ion (P = 0.01; 12.8 ± 0.6 nEq/l AczTr, 15.5 ± 0.6 nEq/l Con) and bicarbonate (P = 0.007; 5.5 ± 0.7 mEq/l AczTr, 10.1 ± 1.3 mEq/l Con) differences across the lung were lower in AczTr compared to Con. No difference was observed in weak electrolytes across the lung. Strong ion difference across the lung was lower in AczTr (P = 0.0003; 4.9 ± 0.8 mEq AczTr, 7.5 ± 1.2 mEq Con), which was affected by strong ion changes across the lung with exception of lactate. Conclusions: CO2 and chloride changes in erythrocytes across the lung seem to be the major contributors to acid-base and ions balance in pulmonary circulation in exercising horses. © 2010 EVJ Ltd.