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This Article Full Text Full Text (PDF) All Versions of this Article: 297/3/R648    most recent 00134.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Kiwull-Schöne, H. F. Articles by Teppema, L. J. PubMed PubMed Citation Articles by Kiwull-Schöne, H. F. Articles by Teppema, L. J.

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Methazolamide does not impair respiratory work performance in anesthetized rabbits

¹Department of Physiology, Ruhr-University, Faculty of Medicine, Bochum, Germany; and ²Department of Anesthesiology, Leiden University Medical Center, Leiden, The Netherlands

Submitted 4 March 2009 ; accepted in final form 12 June 2009

In human medicine, the carbonic anhydrase (CA) inhibitor acetazolamide is used to treat irregular breathing disorders. Previously, we demonstrated in the rabbit that this substance stabilized closed-loop gain properties of the respiratory control system, but concomitantly weakened respiratory muscles. Among others, the highly diffusible CA-inhibitor methazolamide differs from acetazolamide in that it fails to activate Ca²⁺-dependent potassium channels in skeletal muscles. Therefore, we aimed to find out, whether or not methazolamide may exert attenuating adverse effects on respiratory muscle performance as acetazolamide. In anesthetized spontaneously breathing rabbits (n = 7), we measured simultaneously the CO₂ responses of tidal phrenic nerve activity, tidal transpulmonary pressure changes, and tidal volume before and after intravenous application of methazolamide at two mean (± SE) cumulative doses of 3.5 ± 0.1 and 20.8 ± 0.4 mg/kg. Similar to acetazolamide, low- and high-dose methazolamide enhanced baseline ventilation by 52 ± 10% and 166 ± 30%, respectively (P < 0.01) and lowered the base excess in a dose-dependent manner by up to 8.3 ± 0.9 mmol/l (P < 0.001). The transmission of a CO₂-induced rise in phrenic nerve activity into volume and/or pressure and, hence, respiratory work performance was 0.27 ± 0.05 ml·kg^–1·kPa·unit^–1 under control conditions, but remained unchanged upon low- or high-dose methazolamide, at 0.30 ± 0.06 and 0.28 ± 0.07 ml·kg^–1·kPa·unit^–1, respectively. We conclude that methazolamide does not cause respiratory muscle weakening at elevated levels of ventilatory drive. This substance (so far not used for medication of respiratory diseases) may thus exert stabilizing influences on breathing control without adverse effects on respiratory muscle function.

control of breathing; metabolic acidosis; acetazolamide; neuromuscular coupling