Factors of lowered respiratory CO2 sensitivity by acetazolamide in anaesthetized rabbits

• Authors: Heidrun Kiwull-Schöne , Luc Teppema , Peter Kiwull
• Languages of publication: EN

Abstracts

EN

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.

Keywords

EN

Acetazolamide; CO2 sensitivity; metabolic acidosis; respiratory muscle fatigue; rabbits

• Publisher: De Gruyter Open
• Journal: Open Medicine
• Year: 2006
• Volume: 1
• Issue: 4
• Pages: 356-369

Dates

published

1 - 12 - 2006

online

24 - 10 - 2006

Contributors

author

Heidrun Kiwull-Schöne

• Department of Physiology, Faculty of Medicine, Ruhr-University, 44780, Bochum, Germany

author

Luc Teppema

• Department of Physiology and Anesthesiology, Leiden University Medical Center, 2300, RC Leiden, The Netherlands

author

Peter Kiwull

• Department of Physiology, Faculty of Medicine, Ruhr-University, 44780, Bochum, Germany

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Identifiers

DOI

10.2478/s11536-006-0034-7