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


OBJECTIVE
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.


CONCLUSIONS
The current data provide comprehensive evidence of in vivo fluid homeostasis in lungs of exercising horses without and with CA inhibition.
Vengust
M
M
Veterinary Faculty, University of Ljubljana, Ljubljana SI- 115, PO Box 3425, Slovenia.
Staempfli
H
H
Viel
L
L
Heigenhauser
G
G
D000086:Acetazolamide / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001784:Blood Gas Analysis / Q000662:veterinary; D001798:Blood Proteins / Q000032:analysis; D001810:Blood Volume / Q000502:physiology / Q000662:veterinary; D002245:Carbon Dioxide / Q000097:blood; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology*; D015633:Extravascular Lung Water / Q000378:metabolism / Q000502:physiology; D005260:Female; D018495:Fluid Shifts / Q000502:physiology; D006736:Horses / Q000097:blood / Q000378:metabolism / Q000502:physiology*; D008168:Lung / Q000502:physiology*; D008297:Male; D010100:Oxygen / Q000097:blood; D010805:Physical Conditioning, Animal / Q000502:physiology*; D011652:Pulmonary Circulation / Q000187:drug effects*; D011659:Pulmonary Gas Exchange / Q000187:drug effects / Q000502:physiology
D001798:Blood Proteins; D002257:Carbonic Anhydrase Inhibitors; D002245:Carbon Dioxide; D000086:Acetazolamide; D010100:Oxygen