Wu Sijin, Chen Zhongli, Gao Yuan, Cai Mengxing, Yang Jiandu, Han Jing, Chen Ruohan, Wu Ying, Dai Yan, Chen Keping
Arrhythmia Center, Fuwai Hospital, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Mass Spectrometry Platform, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Heart Rhythm. 2025 Jul;22(7):1810-1817. doi: 10.1016/j.hrthm.2024.09.047. Epub 2024 Sep 21.
Serotonin is an important neurohormone that regulates vascular tone and autonomic reflexes, though its pathophysiological role in vasovagal syncope (VVS) remains uncertain.
This study sought to explore the involvement of serotonin and serotonergic-related metabolites in the pathogenesis of VVS.
Sixty-six patients [mean age 45.6±17.0 years; 33 women (50%)] 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, and synthesis source tryptophan-were measured using the liquid chromatography tandem mass spectrometry method.
HUTT was positive in 45 (68.2%) patients and negative in 21 (21.8%) patients. Significant differences were observed in plasma 5-HTP and 5-hydroxyindoleacetic acid levels between HUTT-positive and HUTT-negative patients (P<.001 and P=.040, respectively) as well as before and after syncope (P<.001 for all), 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=.037), and a greater change in serotonin correlated with a shorter time to syncope (R=0.38; P=.015). Furthermore, certain serotonergic-related metabolites exhibited significant correlations with hemodynamic changes during VVS episodes, with 5-HTP demonstrating the highest sensitivity.
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.
血清素是一种重要的神经激素，可调节血管张力和自主反射，但其在血管迷走性晕厥（VVS）中的病理生理作用仍不确定。
本研究旨在探讨血清素及血清素相关代谢产物在VVS发病机制中的作用。
66例复发性VVS患者[平均年龄45.6±17.0岁；33例女性（50%）]接受了直立倾斜试验（HUTT）。所有患者均在静息仰卧位采集血样，HUTT阳性患者在晕厥期间额外采集一份血样。采用液相色谱串联质谱法测定血浆和血小板血清素水平以及血清素相关代谢产物的血浆浓度，这些代谢产物包括血清素的前体5-羟色氨酸（5-HTP）、主要代谢产物5-羟吲哚乙酸以及合成来源色氨酸。
45例（68.2%）患者HUTT阳性，21例（21.8%）患者HUTT阴性。HUTT阳性和阴性患者之间以及晕厥前后血浆5-HTP和5-羟吲哚乙酸水平存在显著差异（分别为P<0.001和P=0.040），而血清素和色氨酸水平无显著变化。值得注意的是，无药物治疗的VVS患者在晕厥期间血浆血清素水平显著升高（P=0.037），血清素的更大变化与晕厥时间缩短相关（R=0.38；P=0.015）。此外，某些血清素相关代谢产物与VVS发作期间的血流动力学变化显著相关，其中5-HTP显示出最高的敏感性。
尽管血浆和血小板血清素水平未改变，但某些血清素相关代谢产物在VVS发作期间显著变化并与血流动力学参数相关，提示血清素代谢途径改变可能参与VVS的发病机制。
