Effects of chronic acetazolamide administration on gas exchange and acid-base control in pulmonary circulation in exercising horses.
BACKGROUND
Carbonic anhydrase (CA) catalyses the hydration/dehydration reaction of CO(2) and increases the rate of Cl(-) and HCO(3)(-) exchange between the erythrocytes and plasma. Therefore, chronic inhibition of CA has a potential to attenuate CO(2) output and induce greater metabolic and respiratory acidosis in exercising horses.


OBJECTIVE
To determine the effects of Carbonic anhydrase inhibition on CO(2) 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 CO(2) 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 CO(2) output was lower in AczTr (P < 0.0001). Arterial PCO(2) (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
CO(2) 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.
Firestone Equine Respiratory Research Laboratory, University of Guelph, Ontario, Canada. modest.vengust@vf.uni-lj.si
M
M
Vengust
H
H
Stämpfli
A N
AN
De Moraes
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F
Teixeiro-Neto
L
L
Viel
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G
Heigenhauser
D000086:Acetazolamide / Q000008:administration & dosage / Q000494:pharmacology*; D000136:Acid-Base Equilibrium / Q000187:drug effects*; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D002245:Carbon Dioxide / Q000097:blood; D004334:Drug Administration Schedule; D004912:Erythrocytes / Q000502:physiology; D005260:Female; D006400:Hematocrit / Q000662:veterinary; D006454:Hemoglobins / Q000378:metabolism; D006736:Horses / Q000097:blood / Q000502:physiology*; D008297:Male; D010313:Partial Pressure; D010805:Physical Conditioning, Animal / Q000502:physiology*; D010807:Physical Endurance / Q000502:physiology; D011659:Pulmonary Gas Exchange / Q000187:drug effects*; D013997:Time Factors
D001798:Blood Proteins; D006454:Hemoglobins; D002245:Carbon Dioxide; D000086:Acetazolamide