Comparative effects of glyceryl trinitrate and amyl nitrite on pulse wave reflection and augmentation index

Authors

  • Lynn D. Greig,

    1. Centre for Cardiovascular Science, The University of Edinburgh, Western General Hospital, Edinburgh, UK and
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  • Stephen J. Leslie,

    1. Centre for Cardiovascular Science, The University of Edinburgh, Western General Hospital, Edinburgh, UK and
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  • Fraser W. Gibb,

    1. Centre for Cardiovascular Science, The University of Edinburgh, Western General Hospital, Edinburgh, UK and
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  • Sherilyn Tan,

    1. Centre for Cardiovascular Science, The University of Edinburgh, Western General Hospital, Edinburgh, UK and
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  • David E. Newby,

    1. Royal Infirmary of Edinburgh, Edinburgh, UK
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  • David J. Webb

    Corresponding author
    1. Centre for Cardiovascular Science, The University of Edinburgh, Western General Hospital, Edinburgh, UK and
      Professor D. J. Webb, Clinical Research Centre, The University of Edinburgh, Western General Hospital, Edinburgh, EH4 2XU, UK. Tel.: + 44 (0)131 537 2006 Fax: + 44 (0)870 134 0897 E-mail: d.j.webb@ed.ac.uk
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Professor D. J. Webb, Clinical Research Centre, The University of Edinburgh, Western General Hospital, Edinburgh, EH4 2XU, UK. Tel.: + 44 (0)131 537 2006 Fax: + 44 (0)870 134 0897 E-mail: d.j.webb@ed.ac.uk

Abstract

Aims

The influence of vasodilators on augmentation index (AIx) offers a simple, rapid and noninvasive method of evaluating vascular function. Glyceryl trinitrate (GTN) is widely used as an endothelium-independent vasodilator, although other nitrates that are shorter acting may have advantages in clinical studies. The aim of this study was to compare the effects of two short-acting nitrates, GTN and amyl nitrite, which have differing pharmacodynamic profiles.

Methods

Twenty-one healthy volunteers (15 male; mean age 35 years, range 21–56 years) attended on three occasions and received sublingual GTN (0.5 mg for 3 min), inhaled amyl nitrite (0.2 ml inhaled for 30 s), or no treatment in a randomized cross-over design. Haemodynamic responses of AIx, blood pressure and thoracic bioimpedance (heart rate, cardiac index) were assessed by measurement at baseline, every 60 s for the first 5 min, and then every 5 min for a further 55 min.

Results

AIx was reduced by amyl nitrite (peak effect −9 ± 2% at 1 min, P < 0.002) and GTN (peak effect −12 ± 3% at 4 min, P < 0.05). Compared with amyl nitrite, the onset and offset of action of GTN was slower. Amyl nitrite initially increased heart rate by 27 ± 4% (P < 0.001) and cardiac index by 13 ± 3% (P < 0.001) whereas GTN had no significant effect (P > 0.05). Neither agent affected blood pressure.

Conclusions

GTN causes a slower and more sustained reduction in AIx than amyl nitrite. Although amyl nitrite causes a more rapid fall and recovery in AIx, it induces a reflex tachycardia that may limit interpretation of the initial (1 min) but not later (2 min) changes in AIx. The prolonged offset of GTN suggests that a sufficient washout period must be included when making repeated measures or when assessing the subsequent effects of other agents.

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