Factors of lowered respiratory CO2 sensitivity by acetazolamide in anaesthetized rabbits
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The carbonic anhydrase (CA) inhibitor acetazolamide is a classic drug to treat patients with breathing disorders. Recent studies in rabbits showed that low-dose acetazolamide (not causing appreciable inhibition of red cell CA) significantly weakened respiratory muscle performance, accompanied by diminished ventilatory CO2-sensitivity, which implies stabilizing loop-gain properties. Now is aimed to explore the interaction of these factors under conditions of complete CA-inhibition by acetazolamide in a higher dose-range.In anesthetized rabbits (N=7), acetazolamide (up to 75 mg·kg−1) distinctly lowered the base excess (to-7.6 ± 0.9mM, mean ± SEM) without respiratory compensation of arterial pH. Ventilatory CO2-sensitivity was nearly abolished to 15.1 ± 5.2% of control, but the transmission of a CO2-mediated rise in tidal phrenic activity into respiratory work was only reduced by 51.6 ± 6.4%, P < 0.001, not very much more than (~38%) already observed at low-doses.Thus, the large reduction of ventilatory CO2-sensitivity in the high-dose range cannot be ascribed to respiratory muscle weakening, but rather may relate to complete inhibition of red cell CA. Conversely, CA-inhibition may not be the only cause for the weakening effect of acetazolamide on (respiratory) muscles. Adverse effects on respiratory muscles, impaired CO2-transport and acid-base imbalance may limit to make use of stabilizing effects on breathing control functions by high-dose acetazolamide.
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