{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T06:31:18Z","timestamp":1775025078000,"version":"3.50.1"},"reference-count":68,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,7,19]],"date-time":"2023-07-19T00:00:00Z","timestamp":1689724800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:p><jats:bold>Introduction:<\/jats:bold> 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\u2019 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.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> We measured peripheral chemoreceptors\u2019 sensitivity using hypoxic ventilatory response (HVR), central chemoreceptors\u2019 sensitivity using hypercapnic hyperoxic ventilatory response (HCVR), and dyspnea severity before and 4 \u00b1 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 <jats:ext-link>ClinicalTrials.com<\/jats:ext-link> at NCT05080478.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Ticagrelor significantly increased both HVR (0.52 \u00b1 0.46 vs. 0.84 \u00b1 0.69 L min<jats:sup>-1<\/jats:sup>\u00a0%<jats:sup>\u22121<\/jats:sup>; <jats:italic>p &amp;lt; 0.01<\/jats:italic>) and HCVR (1.05 \u00b1 0.64 vs. 1.75 \u00b1 1.04\u00a0L\u00a0min<jats:sup>\u22121<\/jats:sup>\u00a0mmHg<jats:sup>\u22121<\/jats:sup>; <jats:italic>p &amp;lt; 0.01<\/jats:italic>). The absolute change in HVR correlated with the change in HCVR. Clopidogrel administration did not significantly influence HVR (0.63 \u00b1 0.32 vs. 0.58 \u00b1 0.33 L min<jats:sup>-1<\/jats:sup>%<jats:sup>\u22121<\/jats:sup>; <jats:italic>p = 0.53<\/jats:italic>) and HCVR (1.22 \u00b1 0.67 vs. 1.2 \u00b1 0.64\u00a0L\u00a0min<jats:sup>\u22121<\/jats:sup>\u00a0mmHg<jats:sup>\u22121<\/jats:sup>; <jats:italic>p = 0.79<\/jats:italic>). 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.<\/jats:p><jats:p><jats:bold>Discussion:<\/jats:bold> 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.<\/jats:p>","DOI":"10.3389\/fphys.2023.1214893","type":"journal-article","created":{"date-parts":[[2023,7,19]],"date-time":"2023-07-19T09:44:09Z","timestamp":1689759849000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["The effects of P2Y12 adenosine receptors\u2019 inhibitors on central and peripheral chemoreflexes"],"prefix":"10.3389","volume":"14","author":[{"given":"Stanislaw","family":"Tubek","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Piotr","family":"Niewinski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Langner-Hetmanczuk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maksym","family":"Jura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wiktor","family":"Kuliczkowski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krzysztof","family":"Reczuch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Piotr","family":"Ponikowski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,7,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"4269","DOI":"10.1113\/jphysiol.2012.237800","article-title":"Hypertension is critically dependent on the carotid body input in the spontaneously hypertensive rat","volume":"590","author":"Abdala","year":"2012","journal-title":"J. physiology"},{"key":"B68","doi-asserted-by":"publisher","first-page":"632","DOI":"10.1080\/00015385.2021.1973770","article-title":"Ticagrelor improves systemic immune-inflammation index in acute coronary syndrome patients","volume":"77","author":"Adali","year":"2022","journal-title":"Acta Cardiol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"A2484","DOI":"10.1164\/ajrccm-conference.2011.183.1_MeetingAbstracts.A2484","article-title":"Atp inhibits carotid body glomus cell hypoxia response via P2y12 receptors","volume":"183","author":"Agarwal","year":"2011","journal-title":"Am. 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