Effects of chronic acetazolamide administration on fluid flux from the pulmonary vasculature at rest and during exercise in horses

REASONS FOR PERFORMING STUDY: Horses develop high pulmonary pressures during exercise, which force fluid out of pulmonary capillaries. Specific airway diseases in horses, especially those associated with hypoxaemia, hypercapnoea and acidosis may influence pulmonary haemodynamics and pulmonary interstitial fluid equilibrium. OBJECTIVES: This study was designed to determine fluid flux (J(V-A) l/min) across the lung in exercising horses treated chronically with acetazolamide. METHODS: Six horses were exercised on a treadmill until fatigue without (Con) and with chronic carbonic anhydrase (CA) inhibition (AczTr) and associated hypercapnoea and acidosis. Carbonic anhydrase inhibition was achieved with administration of acetazolamide (Acz). Arterial and mixed venous blood were sampled, and VCO2 and VO2 measured. Blood volume changes across the lung (deltaBV%) were calculated from changes in plasma protein, haemoglobin and packed cell volume (PCV). Cardiac output (Q) was calculated using Fick principle. J(V-A) across the alveolar-capillary barrier was then quantified based on Q and deltaBV. Variables were analysed using 2-way repeated-measures ANOVA (P<0.05). A significant F ratio was further analysed using Tukey post hoc analysis. RESULTS: Treatment had a significant effect on J(V-A) (P = 0.002). At rest there was no J(V-A) in Con (0.63 +/- 0.6 l/min) and AczTr (0.84 +/- 0.3 l/min). During exercise Con fluid moved from the pulmonary circulation into the pulmonary interstitium (mean +/- s.e. J(V-A) 9.4 +/- 2.4 l/min). This was different from AczTr (mean +/- s.e. J(V-A) 1.8 +/- 1.9 l/min), where no transvascular fluxes from pulmonary circulation were present during exercise (P = 0.008). CONCLUSIONS: Chronic Acz treatment with associated hypercapnoea and acidosis affects J(V-A) in lungs of exercising horses. Lung fluid dynamics adapted to hypercapnoea and acidosis with reduction of fluid flow from the pulmonary circulation. POTENTIAL RELEVANCE: The current data provide comprehensive evidence of in vivo fluid homeostasis in lungs of exercising horses without and with CA inhibition.