{"title":"The role of serotonin and serotonergic-related metabolites in pathogenesis of vasovagal syncope.","authors":"Sijin Wu, Zhongli Chen, Yuan Gao, Mengxing Cai, Jiandu Yang, Jing Han, Ruohan Chen, Ying Wu, Yan Dai, Keping Chen","doi":"10.1016/j.hrthm.2024.09.047","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Serotonin is an important neurohormone that regulates vascular tone and autonomic reflexes, though its pathophysiological role in vasovagal syncope (VVS) remains uncertain.</p><p><strong>Objective: </strong>This study sought to explore the involvement of serotonin and serotonergic-related metabolites in the pathogenesis of VVS.</p><p><strong>Methods: </strong>Sixty-six patients (age 45.6±17.0 years; 33 females) with recurrent VVS underwent a head-up tilt test (HUTT). Blood samples were collected from all patients in a resting supine position, with an additional sample obtained from HUTT-positive patients during syncope. Plasma and platelet serotonin levels, and plasma concentrations of serotonergic-related metabolites-including serotonin's precursor 5-hydroxytryptophan (5-HTP), major metabolite 5-hydroxyindoleacetic acid (5-HIAA), and synthesis source tryptophan-were measured using the liquid chromatography tandem mass spectrometry (LC-MS/MS) method.</p><p><strong>Results: </strong>HUTT was positive in 45 patients and negative in 21 patients. Significant differences were observed in plasma 5-HTP and 5-HIAA levels between HUTT+ and HUTT- patients (P<0.001 and P=0.040, respectively), as well as before and after syncope (all P<0.001), whereas no significant changes were found in serotonin and tryptophan levels. Notably, plasma serotonin levels significantly increased during syncope in patients with drug-free VVS (P=0.037), and a greater change in serotonin correlated with a shorter time to syncope (R<sup>2</sup>=0.38, P=0.015). Furthermore, certain serotonergic-related metabolites exhibited significant correlations with hemodynamic changes during VVS episodes, with 5-HTP demonstrating the highest sensitivity.</p><p><strong>Conclusions: </strong>Despite the unchanged plasma and platelet serotonin levels, certain serotonergic-related metabolites significantly changed and correlated with hemodynamic parameters during VVS episodes, suggesting the potential involvement of an altered serotonergic metabolic pathway in VVS.</p>","PeriodicalId":12886,"journal":{"name":"Heart rhythm","volume":null,"pages":null},"PeriodicalIF":5.6000,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Heart rhythm","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.hrthm.2024.09.047","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Serotonin is an important neurohormone that regulates vascular tone and autonomic reflexes, though its pathophysiological role in vasovagal syncope (VVS) remains uncertain.
Objective: This study sought to explore the involvement of serotonin and serotonergic-related metabolites in the pathogenesis of VVS.
Methods: Sixty-six patients (age 45.6±17.0 years; 33 females) with recurrent VVS underwent a head-up tilt test (HUTT). Blood samples were collected from all patients in a resting supine position, with an additional sample obtained from HUTT-positive patients during syncope. Plasma and platelet serotonin levels, and plasma concentrations of serotonergic-related metabolites-including serotonin's precursor 5-hydroxytryptophan (5-HTP), major metabolite 5-hydroxyindoleacetic acid (5-HIAA), and synthesis source tryptophan-were measured using the liquid chromatography tandem mass spectrometry (LC-MS/MS) method.
Results: HUTT was positive in 45 patients and negative in 21 patients. Significant differences were observed in plasma 5-HTP and 5-HIAA levels between HUTT+ and HUTT- patients (P<0.001 and P=0.040, respectively), as well as before and after syncope (all P<0.001), whereas no significant changes were found in serotonin and tryptophan levels. Notably, plasma serotonin levels significantly increased during syncope in patients with drug-free VVS (P=0.037), and a greater change in serotonin correlated with a shorter time to syncope (R2=0.38, P=0.015). Furthermore, certain serotonergic-related metabolites exhibited significant correlations with hemodynamic changes during VVS episodes, with 5-HTP demonstrating the highest sensitivity.
Conclusions: Despite the unchanged plasma and platelet serotonin levels, certain serotonergic-related metabolites significantly changed and correlated with hemodynamic parameters during VVS episodes, suggesting the potential involvement of an altered serotonergic metabolic pathway in VVS.
期刊介绍:
HeartRhythm, the official Journal of the Heart Rhythm Society and the Cardiac Electrophysiology Society, is a unique journal for fundamental discovery and clinical applicability.
HeartRhythm integrates the entire cardiac electrophysiology (EP) community from basic and clinical academic researchers, private practitioners, engineers, allied professionals, industry, and trainees, all of whom are vital and interdependent members of our EP community.
The Heart Rhythm Society is the international leader in science, education, and advocacy for cardiac arrhythmia professionals and patients, and the primary information resource on heart rhythm disorders. Its mission is to improve the care of patients by promoting research, education, and optimal health care policies and standards.