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Integrative |
1 Department of Anaesthesiology, Leiden University Medical Center, Leiden, the Netherlands
The carbonic anhydrase inhibitor acetazolamide may have both inhibitory and stimulatory effects on breathing. In this placebo-controlled double-blind study we measured the effect of an intravenous dose (4 mg kg–1) of this agent on the acute isocapnic hypoxic ventilatory response in 16 healthy volunteers (haemoglobin oxygen saturation 83–85%) and examined whether its inhibitory effects on this response could be reversed by antioxidants (1 g ascorbic acid I.V. and 200 mg 
-tocopherol P.O.). The subjects were randomly divided into an antioxidant (Aox) and placebo group. In the Aox group, acetazolamide reduced the mean normocapnic and hypercapnic hypoxic responses by 37% (P < 0.01) and 55% (P < 0.01), respectively, and abolished the O2–CO2 interaction, i.e. the increase in O2 sensitivity with rising PCO2. Antioxidants completely reversed this inhibiting effect on the normocapnic hypoxic response, while in hypercapnia the reversal was partial. In the placebo group, acetazolamide reduced the normo- and hypercapnic hypoxic responses by 33 and 47%, respectively (P < 0.01 versus control in both cases), and also abolished the O2–CO2 interaction. Placebo failed to reverse these inhibitory effects of acetazolamide in this group. We hypothesize that either an isoform of carbonic anhydrase may be involved in the regulation of the redox state in the carotid bodies or that acetazolamide and antioxidants exert independent effects on oxygen-sensing cells, in which both carbonic anhydrase and potassium channels may be involved. The novel findings of this study may have clinical implications, for example with regard to a combined use of acetazolamide and antioxidants at high altitude.
(Received 21 December 2005;
accepted after revision 25 January 2006;
first published online 26 January 2006)
Corresponding author L. J. Teppema: Department Anaesthesiology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, the Netherlands. Email: l.j.s.m.teppema{at}lumc.nl
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L. J. Teppema, H. Bijl, B. M. Gourabi, and A. Dahan The carbonic anhydrase inhibitors methazolamide and acetazolamide have different effects on the hypoxic ventilatory response in the anaesthetized cat J. Physiol., July 15, 2006; 574(2): 565 - 572. [Abstract] [Full Text] [PDF]
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