Kiwull-Schöne HF, Li Y, Kiwull PJ, Teppema LJ
Methazolamide does not impair respiratory work performance in anaesthetized rabbits. [JOURNAL ARTICLE]
Am J Physiol Regul Integr Comp Physiol 2009 Jun 24.
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 Ca(2+)-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 anaesthetized 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 (+/-SEM) cumulative doses of 3.5 +/-0.1 and 20.8 +/-0.4 mgkg(-1). Similar to acetazolamide, low- and high-dose methazolamide enhanced base-line 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 mmoll(-1) (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 mlkg(-1)kPaunit(-1) under control conditions, but remained unchanged upon low- or high-dose methazolamide at 0.30 +/-0.06 and 0.28 +/-0.07 mlkg(-1)kPaunit(-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. Key words: methazolamide, control of breathing, metabolic acidosis, respiratory muscle function.
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