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Acetazolamide prevents hypoxic pulmonary vasoconstriction in conscious dogs

¹Experimental Anesthesia, Department of Anesthesiology and Intensive Care Medicine, Campus Virchow-Klinikum, Charité, D-13353 Berlin, Germany; ²Department of Medicine, University of Washington, Seattle, Washington 98108

Submitted 13 November 2003 ; accepted in final form 23 March 2004

Acute hypoxia increases pulmonary arterial pressure and vascular resistance. Previous studies in isolated smooth muscle and perfused lungs have shown that carbonic anhydrase (CA) inhibition reduces the speed and magnitude of hypoxic pulmonary vasoconstriction (HPV). We studied whether CA inhibition by acetazolamide (Acz) is able to prevent HPV in the unanesthetized animal. Ten chronically tracheotomized, conscious dogs were investigated in three protocols. In all protocols, the dogs breathed 21% O₂ for the first hour and then 8 or 10% O₂ for the next 4 h spontaneously via a ventilator circuit. The protocols were as follows: protocol 1: controls given no Acz, inspired O₂ fraction (FI_O2) = 0.10; protocol 2: Acz infused intravenously (250-mg bolus, followed by 167 µg·kg^–1·min^–1 continuously), FI_O2 = 0.10; protocol 3: Acz given as above, but with FI_O2 reduced to 0.08 to match the arterial PO₂ (Pa_O2) observed during hypoxia in controls. Pa_O2 was 37 Torr during hypoxia in controls, mean pulmonary arterial pressure increased from 17 ± 1 to 23 ± 1 mmHg, and pulmonary vascular resistance increased from 464 ± 26 to 679 ± 40 dyn·s^–1·cm^–5 (P < 0.05). In both Acz groups, mean pulmonary arterial pressure was 15 ± 1 mmHg, and pulmonary vascular resistance ranged between 420 and 440 dyn·s^–1·cm^–5. These values did not change during hypoxia. In dogs given Acz at 10% O₂, the arterial Pa_O2 was 50 Torr owing to hyperventilation, whereas in those breathing 8% O₂ the Pa_O2 was 37 Torr, equivalent to controls. In conclusion, Acz prevents HPV in conscious spontaneously breathing dogs. The effect is not due to Acz-induced hyperventilation and higher alveolar PO₂, nor to changes in plasma endothelin-1, angiotensin-II, or potassium, and HPV suppression occurs despite the systemic acidosis with CA inhibition.

hypoxia; high altitude; carbonic anhydrase; endothelin; angiotensin II

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