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J Physiol Volume 579, Number 3, 909-921, March 15, 2007 DOI: 10.1113/jphysiol.2006.120949
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Effect of acetazolamide on pulmonary and muscle gas exchange during normoxic and hypoxic exercise

Amy M. Jonk1, Irene P. van den Berg1, I. Mark Olfert1, D. Walter Wray1, Tatsuya Arai1, Susan R. Hopkins1 and Peter D. Wagner1

1 Department of Medicine, University of California, San Diego, La Jolla, CA 92093-0623, USA

Acetazolamide (ACZ) is used to prevent acute mountain sickness at altitude. Because it could affect O2 transport in several different and potentially conflicting ways, we examined its effects on pulmonary and muscle gas exchange and acid–base status during cycle exercise at ~30, 50 and 90% Formula in normoxia (FIO2 = 0.2093) and acute hypoxia (FIO2 = 0.125). In a double-blind, order-balanced, crossover design, six healthy, trained men (normoxic Formula = 59 ml kg–1 min–1) exercised at both FIO2 values after ACZ (3 doses of 250 mg, 8 h apart) and placebo. One week later this protocol was repeated using the other drug (placebo or ACZ). We measured cardiac output Formula , leg blood flow (LBF), and muscle and pulmonary gas exchange, the latter using the multiple inert gas elimination technique. ACZ did not significantly affect Formula , Formula , LBF or muscle gas exchange. As expected, ACZ led to lower arterial and venous blood [HCO3], pH and lactate levels (P < 0.05), and increased ventilation (P < 0.05). In both normoxia and hypoxia, ACZ resulted in higher arterial PO2 and saturation and a lower alveolar–arterial PO2 difference (AaDO2) due to both less Formula mismatch and less diffusion limitation (P < 0.05). In summary, ACZ improved arterial oxygenation during exercise, due to both greater ventilation and more efficient pulmonary gas exchange. However, muscle gas exchange was unaffected.

(Received 11 September 2006; accepted after revision 9 January 2007; first published online 11 January 2007)
Corresponding author P. D. Wagner: University of California, San Diego, Department of Medicine 0623A, 9500 Gilman Drive, La Jolla, CA 92093-0623, USA. Email: pdwagner{at}ucsd.edu




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