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The sequelae of VVS is caused by an increase in sympathetic tone and heart rate combined with an underfilled left ventricular chamber that leads to stimulation of cardiac afferent C fibers ultimately leading to bradycardia and vasodilation causing a reduction in venous return, cerebral hypoperfusion and VVS. Several treatment options have been tested including physical counter-pressure measures, electrical pacing, cardioneuroblation. Pharmacological interventions and clinical trials for VVS are summarized in this review; however, there is still limited evidence of their efficacy for reducing episodes of VVS. This review will examine studies using animal models of the vasovagal reflex arc to investigate the physiological mechanisms and neurotransmitters associated with VVS, the tilt-table test that induces VVS in patients and the potential sources of cardiac and platelet mediators that can activate cardiac afferent C fibers. This study will also consider how the previously investigated pharmacotherapies provide insight into the multiple mechanisms involved in VVS and propose new targets for the pharmacological treatment of VVS.<\/jats:p>","DOI":"10.1177\/10742484251351140","type":"journal-article","created":{"date-parts":[[2025,6,21]],"date-time":"2025-06-21T02:04:15Z","timestamp":1750471455000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":6,"title":["The Pathophysiology of Vasovagal Syncope and New Approaches to its Pharmacological Treatment"],"prefix":"10.1177","volume":"30","author":[{"given":"Dalyia","family":"Abu-Ghazaleh","sequence":"first","affiliation":[{"name":"School of Pharmacy and Medical Sciences, Griffith University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7915-1781","authenticated-orcid":false,"given":"David A.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Eastern Health Institute"},{"name":"Eastern Health"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3456-7104","authenticated-orcid":false,"given":"Louise","family":"Roberts","sequence":"additional","affiliation":[{"name":"Eastern Health"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0498-4209","authenticated-orcid":false,"given":"Indu","family":"Singh","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Medical Sciences, Griffith University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9879-4985","authenticated-orcid":false,"given":"Vinicius","family":"Cruzat","sequence":"additional","affiliation":[{"name":"Faculty of Health, Southern Cross University, Bilinga, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3677-0608","authenticated-orcid":false,"given":"Roselyn B.","family":"Rose\u2019Meyer","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Medical Sciences, Griffith University"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,6,20]]},"reference":[{"key":"e_1_3_2_2_2","volume-title":"Clinical methods: the history, physical, and laboratory examinations","author":"Kapoor WN","year":"1990","unstructured":"Kapoor WN. 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