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Some syncope may involve multiple etiologies operating in concert, whereas in other cases multiple syncope events may be due to various differing causes at different times. In this communication, we address the current understanding of the principal contributors to syncope pathophysiology including examination of the manner in which concepts evolved, an overview of factors that constitute consciousness and loss of consciousness, and aspects of neurovascular control and communication that are impacted by cerebral hypoperfusion leading to syncope. Emphasis focuses on 1) current understanding of the way transient systemic hypotension impacts brain blood flow and brain function; 2) the complexity and temporal sequence of vascular, humoral, and cardiac factors that may accompany the most common causes of syncope; 3) the range of circumstances and disease states that may lead to syncope; and 4) clinical features associated with syncope and in particular the reflex syncope syndromes.<\/jats:p>","DOI":"10.1152\/physrev.00007.2024","type":"journal-article","created":{"date-parts":[[2024,8,15]],"date-time":"2024-08-15T13:13:00Z","timestamp":1723727580000},"page":"209-266","update-policy":"https:\/\/doi.org\/10.1152\/aps-crossmark-policy","source":"Crossref","is-referenced-by-count":22,"title":["Pathophysiology of syncope: current concepts and their development"],"prefix":"10.1152","volume":"105","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8511-6920","authenticated-orcid":false,"given":"David G.","family":"Benditt","sequence":"first","affiliation":[{"name":"University of Minnesota Medical School, Minneapolis, Minnesota, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5352-6327","authenticated-orcid":false,"given":"Artur","family":"Fedorowski","sequence":"additional","affiliation":[{"name":"Karolinska Institute, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5710-1094","authenticated-orcid":false,"given":"Richard","family":"Sutton","sequence":"additional","affiliation":[{"name":"Imperial College, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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