Effects of acetazolamide on cerebrovascular function and breathing stability at 5050 m.

Details

Serval ID
serval:BIB_AF42CE2CCF69
Type
Article: article from journal or magazin.
Collection
Publications
Title
Effects of acetazolamide on cerebrovascular function and breathing stability at 5050 m.
Journal
Journal of Physiology
Author(s)
Fan J.L., Burgess K.R., Thomas K.N., Lucas S.J., Cotter J.D., Kayser B., Peebles K.C., Ainslie P.N.
ISSN
1469-7793 (Electronic)
ISSN-L
0022-3751
Publication state
Published
Issued date
2012
Volume
590
Number
Pt 5
Pages
1213-1225
Language
english
Abstract
One of the many actions of the carbonic anhydrase inhibitor, acetazolamide (ACZ), is to accelerate acclimatisation and reduce periodic breathing during sleep. The mechanism(s) by which ACZ may improve breathing stability, especially at high altitude, remain unclear. We tested the hypothesis that acute I.V. ACZ would enhance cerebrovascular reactivity to CO₂ at altitude, and thereby lower ventilatory drive and improve breathing stability during wakefulness. We measured arterial blood gases, minute ventilation (˙VE) and middle cerebral artery blood flow velocity (MCAv) before and 30 min following ACZ administration (I.V. 10 mg kg⁻¹) in 12 healthy participants at sea level and following partial acclimatisation to altitude (5050 m).Measures were made at rest and during changes in end-tidal PCO₂ and PO₂ (isocapnic hypoxia). At sea level, ACZ increased resting MCAv and its reactivity to both hypocapnia and hypercapnia (P < 0.05), and lowered resting VE, arterial O₂ saturation (Sa,O₂ ) and arterial PO₂ (Pa,O₂) (P < 0.05); arterial PCO₂ (Pa,CO₂ ) was unaltered (P > 0.05). At altitude, ACZ also increased resting MCAv and its reactivity to both hypocapnia and hypercapnia (resting MCAv and hypocapnia reactivity to a greater extent than at sea level). Moreover, ACZ at altitude elevated Pa,CO₂ and again lowered resting Pa,O₂ and Sa,O₂ (P <0.05). Although the ˙VE sensitivity to hypercapnia or isocapnic hypoxia was unaltered following ACZ at both sea level and altitude (P > 0.05), breathing stability at altitude was improved (e.g. lower incidence of ventilatory oscillations and variability of tidal volume; P < 0.05). Our data indicate that I.V. ACZ elevates cerebrovascular reactivity and improves breathing stability at altitude, independent of changes in peripheral or central chemoreflex sensitivities. We speculate that Pa,CO₂-mediated elevations in cerebral perfusion and an enhanced cerebrovascular reactivity may partly account for the improved breathing stability following ACZ at high altitude.
Keywords
Acetazolamide/pharmacology, Adult, Altitude, Blood Gas Analysis, Brain/blood supply, Brain/drug effects, Carbon Dioxide/physiology, Carbonic Anhydrase Inhibitors/pharmacology, Cerebral Arteries/drug effects, Cerebral Arteries/physiology, Cerebrovascular Circulation/drug effects, Female, Humans, Male, Pulmonary Ventilation/drug effects, Regional Blood Flow/drug effects, Respiration/drug effects, Young Adult
Pubmed
Web of science
Create date
25/09/2013 12:31
Last modification date
20/08/2019 15:18
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