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Influence of indomethacin on the ventilatory and cerebrovascular responsiveness to hypoxia

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Abstract

Indomethacin (INDO) has the potential to be a useful tool to explore the influence of cerebral blood flow and its responses to CO2 on ventilatory control. However, the effect of INDO on the cerebrovascular and ventilatory response to hypoxia remains unclear; therefore, we examined the effect of INDO on ventilatory and cerebrovascular sensitivity to hypoxia and hypercapnia. We measured end-tidal gases, ventilation \( (\dot{V}_{\text{E}} ), \) and middle cerebral artery velocity (MCAv) before and 90 min following INDO (100 mg) in 12 healthy participants at rest and during hyperoxic hypercapnia and isocapnic hypoxia. Following INDO, resting \( \dot{V}_{\text{E}} \) and end-tidal gases were unaltered (P > 0.05), whilst MCAv was lowered by 25 ± 19% (P < 0.001). INDO ingestion reduced MCAv-CO2 reactivity by 46 ± 29% (2.9 ± 0.9 vs. 1.7 ± 0.9 cm s−1 mmHg−1; P < 0.001) and enhanced the \( \dot{V}_{\text{E}} \)-CO2 sensitivity by 0.5 ± 0.5 L min−1 mmHg−1 (1.9 ± 1.5 vs. 2.3 ± 1.6 L min−1 mmHg−1; P < 0.05). No changes were observed in either the MCAv or \( \dot{V}_{\text{E}} \) responsiveness to isocapnic hypoxia following INDO ingestion (P > 0.05). These findings indicate that INDO does not alter cerebrovascular and ventilatory responsiveness to hypoxia, indicating a preserved peripheral chemoreflex in response to this pharmacological agent.

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Acknowledgments

The authors are thankful to Prof. J. Duffin who kindly provided his technical assistance in the rebreathing analysis programme. Special thanks are due to our participants for giving their time for this study. We also extend our thanks to ADInstruments for the use of their laboratory equipment. This study was supported by the Otago Medical Research Foundation, SPARC New Zealand and Peninsula Health Care p/l.

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Authors and Affiliations

  1. Department of Physiology, Otago School of Medical Science, University of Otago, Dunedin, New Zealand

    Jui-Lin Fan, Kate N. Thomas, Karen C. Peebles, Samuel J. E. Lucas & Rebekah A. I. Lucas

  2. Department of Medicine, University of Sydney, Sydney, NSW, Australia

    Keith R. Burgess

  3. School of Physical Education, University of Otago, Dunedin, New Zealand

    Samuel J. E. Lucas, Rebekah A. I. Lucas & James D. Cotter

  4. Department of Health and Human Kinetics, Faculty of Health and Social Development, University of British Columbia Okanagan, Kelowna, Canada

    Philip N. Ainslie

  5. Institute of Movement Sciences and Sports Medicine, University of Geneva, Geneva, Switzerland

    Jui-Lin Fan

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  1. Jui-Lin Fan
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Fan, JL., Burgess, K.R., Thomas, K.N. et al. Influence of indomethacin on the ventilatory and cerebrovascular responsiveness to hypoxia. Eur J Appl Physiol 111, 601–610 (2011). https://doi.org/10.1007/s00421-010-1679-0

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