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The effects of P2Y(12) adenosine receptors’ inhibitors on central and peripheral chemoreflexes
Introduction: The most common side effect of ticagrelor is dyspnea, which leads to premature withdrawal of this life-saving medication in 6.5% of patients. Increased chemoreceptors’ sensitivity was suggested as a possible pathophysiological explanation of this phenomenon; however, the link between o...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10394699/ https://www.ncbi.nlm.nih.gov/pubmed/37538377 http://dx.doi.org/10.3389/fphys.2023.1214893 |
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author | Tubek, Stanislaw Niewinski, Piotr Langner-Hetmanczuk, Anna Jura, Maksym Kuliczkowski, Wiktor Reczuch, Krzysztof Ponikowski, Piotr |
author_facet | Tubek, Stanislaw Niewinski, Piotr Langner-Hetmanczuk, Anna Jura, Maksym Kuliczkowski, Wiktor Reczuch, Krzysztof Ponikowski, Piotr |
author_sort | Tubek, Stanislaw |
collection | PubMed |
description | Introduction: The most common side effect of ticagrelor is dyspnea, which leads to premature withdrawal of this life-saving medication in 6.5% of patients. Increased chemoreceptors’ sensitivity was suggested as a possible pathophysiological explanation of this phenomenon; however, the link between oversensitization of peripheral and/or central chemosensory areas and ticagrelor intake has not been conclusively proved. Methods: We measured peripheral chemoreceptors’ sensitivity using hypoxic ventilatory response (HVR), central chemoreceptors’ sensitivity using hypercapnic hyperoxic ventilatory response (HCVR), and dyspnea severity before and 4 ± 1 weeks following ticagrelor initiation in 11 subjects with chronic coronary syndrome undergoing percutaneous coronary intervention (PCI). The same tests were performed in 11 age-, sex-, and BMI-matched patients treated with clopidogrel. The study is registered at ClinicalTrials.com at NCT05080478. Results: Ticagrelor significantly increased both HVR (0.52 ± 0.46 vs. 0.84 ± 0.69 L min(-1) %(−1); p < 0.01) and HCVR (1.05 ± 0.64 vs. 1.75 ± 1.04 L min(−1) mmHg(−1); p < 0.01). The absolute change in HVR correlated with the change in HCVR. Clopidogrel administration did not significantly influence HVR (0.63 ± 0.32 vs. 0.58 ± 0.33 L min(-1)%(−1); p = 0.53) and HCVR (1.22 ± 0.67 vs. 1.2 ± 0.64 L min(−1) mmHg(−1); p = 0.79). Drug-related dyspnea was reported by three subjects in the ticagrelor group and by none in the clopidogrel group. These patients were characterized by either high baseline HVR and HCVR or excessive increase in HVR following ticagrelor initiation. Discussion: Ticagrelor, contrary to clopidogrel, sensitizes both peripheral and central facets of chemodetection. Two potential mechanisms of ticagrelor-induced dyspnea have been identified: 1) high baseline HVR and HCVR or 2) excessive increase in HVR or HVR and HCVR. Whether other patterns of changes in chemosensitivities play a role in the pathogenesis of this phenomenon needs to be further investigated. |
format | Online Article Text |
id | pubmed-10394699 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-103946992023-08-03 The effects of P2Y(12) adenosine receptors’ inhibitors on central and peripheral chemoreflexes Tubek, Stanislaw Niewinski, Piotr Langner-Hetmanczuk, Anna Jura, Maksym Kuliczkowski, Wiktor Reczuch, Krzysztof Ponikowski, Piotr Front Physiol Physiology Introduction: The most common side effect of ticagrelor is dyspnea, which leads to premature withdrawal of this life-saving medication in 6.5% of patients. Increased chemoreceptors’ sensitivity was suggested as a possible pathophysiological explanation of this phenomenon; however, the link between oversensitization of peripheral and/or central chemosensory areas and ticagrelor intake has not been conclusively proved. Methods: We measured peripheral chemoreceptors’ sensitivity using hypoxic ventilatory response (HVR), central chemoreceptors’ sensitivity using hypercapnic hyperoxic ventilatory response (HCVR), and dyspnea severity before and 4 ± 1 weeks following ticagrelor initiation in 11 subjects with chronic coronary syndrome undergoing percutaneous coronary intervention (PCI). The same tests were performed in 11 age-, sex-, and BMI-matched patients treated with clopidogrel. The study is registered at ClinicalTrials.com at NCT05080478. Results: Ticagrelor significantly increased both HVR (0.52 ± 0.46 vs. 0.84 ± 0.69 L min(-1) %(−1); p < 0.01) and HCVR (1.05 ± 0.64 vs. 1.75 ± 1.04 L min(−1) mmHg(−1); p < 0.01). The absolute change in HVR correlated with the change in HCVR. Clopidogrel administration did not significantly influence HVR (0.63 ± 0.32 vs. 0.58 ± 0.33 L min(-1)%(−1); p = 0.53) and HCVR (1.22 ± 0.67 vs. 1.2 ± 0.64 L min(−1) mmHg(−1); p = 0.79). Drug-related dyspnea was reported by three subjects in the ticagrelor group and by none in the clopidogrel group. These patients were characterized by either high baseline HVR and HCVR or excessive increase in HVR following ticagrelor initiation. Discussion: Ticagrelor, contrary to clopidogrel, sensitizes both peripheral and central facets of chemodetection. Two potential mechanisms of ticagrelor-induced dyspnea have been identified: 1) high baseline HVR and HCVR or 2) excessive increase in HVR or HVR and HCVR. Whether other patterns of changes in chemosensitivities play a role in the pathogenesis of this phenomenon needs to be further investigated. Frontiers Media S.A. 2023-07-19 /pmc/articles/PMC10394699/ /pubmed/37538377 http://dx.doi.org/10.3389/fphys.2023.1214893 Text en Copyright © 2023 Tubek, Niewinski, Langner-Hetmanczuk, Jura, Kuliczkowski, Reczuch and Ponikowski. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Physiology Tubek, Stanislaw Niewinski, Piotr Langner-Hetmanczuk, Anna Jura, Maksym Kuliczkowski, Wiktor Reczuch, Krzysztof Ponikowski, Piotr The effects of P2Y(12) adenosine receptors’ inhibitors on central and peripheral chemoreflexes |
title | The effects of P2Y(12) adenosine receptors’ inhibitors on central and peripheral chemoreflexes |
title_full | The effects of P2Y(12) adenosine receptors’ inhibitors on central and peripheral chemoreflexes |
title_fullStr | The effects of P2Y(12) adenosine receptors’ inhibitors on central and peripheral chemoreflexes |
title_full_unstemmed | The effects of P2Y(12) adenosine receptors’ inhibitors on central and peripheral chemoreflexes |
title_short | The effects of P2Y(12) adenosine receptors’ inhibitors on central and peripheral chemoreflexes |
title_sort | effects of p2y(12) adenosine receptors’ inhibitors on central and peripheral chemoreflexes |
topic | Physiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10394699/ https://www.ncbi.nlm.nih.gov/pubmed/37538377 http://dx.doi.org/10.3389/fphys.2023.1214893 |
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