Brunetta Enrico, Shiffer Dana, Mandelli Pietro, Achenza Sara, Folci Marco, Zumbo Aurora, Minonzio Maura, Cairo Beatrice, Jacob Giris, Boccassini Laura, Puttini Piercarlo Sarzi, Porta Alberto, Furlan Raffaello
Department of Internal Medicine, Humanitas Clinical and Research Center - IRCCS, Milan University, Milan, Italy.
Department of Pathophysiology and Transplantation, Faculty of Medicine and Surgery, University of Milan, Milan, Italy.
Front Physiol. 2019 Aug 27;10:1104. doi: 10.3389/fphys.2019.01104. eCollection 2019.
Primary Sjögren's syndrome (pSS) is an autoimmune disease affecting exocrine glands and extra-glandular organs. There are conflicting reports on the presence of autonomic dysfunction in pSS and no data are available on the functional status of sympathetic outflow to the vessels and baroreceptor [baroreflex sensitivity (BRS)] control mechanisms. We investigated the cardiac (cBRS) and sympathetic (sBRS) baroreceptor modulation in both time and frequency domains and the cardiovascular autonomic profile in pSS patients compared to healthy controls. Autonomic symptoms were quantified by the Composite Autonomic Symptom Scale (COMPASS31) three-item questionnaire. The EULAR Sjogren's syndrome patient reported index (ESSPRI) questionnaire evaluated the magnitude of pSS clinical symptoms, i.e., fatigue, pain, and sicca symptoms. Electrocardiogram, beat-by-beat arterial pressure (AP) and respiratory activity were continuously recorded in 17 pSS patients and 16 healthy controls, while supine and during 75° head-up tilt. In seven patients and seven controls, muscle sympathetic nerve activity (MSNA) was measured. Spectrum analysis of RR variability provided markers of cardiac vagal modulation (HF nu) and sympatho-vagal balance [low frequency (LF)/high frequency (HF)]. The power of LF (0.1 Hz) oscillations of systolic arterial pressure (SAP) variability (LF) evaluated the vasomotor response to sympathetic stimulation. Compared to controls, pSS patients scored higher in total COMPASS31 ( < 0.0001) and all ESSPRI subdomains (fatigue, = 0.005; pain, = 0.0057; dryness, < 0.0001). Abnormal scialometry (<1.5 ml/15 min) and Schirmer tests (<5 mm/5 min) were found in pSS patients and salivary flow rate was negatively associated with ESSPRI dryness ( = 0.0014). While supine, pSS patients had lower SEQ index of cardiac baroreceptor sensitivity, higher HF ( = 0.021), lower LF/HF ( = 0.007), and greater MSNA ( = 0.038) than controls. No differences were observed in LF between groups. During orthostatic challenge, although LF increased similarly in both groups, MSNA was greater in pSS patients ( = 0.003). At rest pSS patients showed lower cBR control and greater parasympathetic modulation. Furthermore, greater sympathetic nerve activity was observed in pSS patients while supine and in response to gravitational challenge. We hypothesized that such enhanced sympathetic vasoconstrictor activity might reflect an attempt to maintain blood pressure in a setting of likely reduced vascular responsiveness.
原发性干燥综合征(pSS)是一种影响外分泌腺和腺外器官的自身免疫性疾病。关于pSS中自主神经功能障碍的存在存在相互矛盾的报道,并且没有关于血管交感神经输出功能状态和压力感受器[压力反射敏感性(BRS)]控制机制的数据。我们在时域和频域研究了pSS患者与健康对照者的心脏(cBRS)和交感神经(sBRS)压力感受器调节以及心血管自主神经特征。通过复合自主神经症状量表(COMPASS31)三项问卷对自主神经症状进行量化。欧洲抗风湿病联盟干燥综合征患者报告指数(ESSPRI)问卷评估了pSS临床症状的严重程度,即疲劳、疼痛和口干症状。在17例pSS患者和16例健康对照者中,在仰卧位和75°头高位倾斜期间连续记录心电图、逐搏动脉压(AP)和呼吸活动。在7例患者和7例对照者中测量了肌肉交感神经活动(MSNA)。RR间期变异性的频谱分析提供了心脏迷走神经调节(HF nu)和交感-迷走平衡[低频(LF)/高频(HF)]的标志物。收缩期动脉压(SAP)变异性(LF)的LF(0.1 Hz)振荡功率评估了对交感神经刺激的血管运动反应。与对照组相比,pSS患者在COMPASS31总分(<0.0001)和所有ESSPRI子域(疲劳,=0.005;疼痛,=0.0057;干燥,<0.0001)中的得分更高。在pSS患者中发现异常的唾液分泌量测定(<1.5 ml/15分钟)和施默试验(<5 mm/5分钟),唾液流速与ESSPRI干燥程度呈负相关(=0.0014)。仰卧位时,pSS患者的心脏压力感受器敏感性SEQ指数较低,HF较高(=0.021),LF/HF较低(=0.007),MSNA大于对照组(=0.038)。两组之间在LF方面未观察到差异。在直立位挑战期间,尽管两组的LF均以相似的幅度增加,但pSS患者的MSNA更大(=0.003)。静息时,pSS患者表现出较低的cBR控制和较强的副交感神经调节。此外,在仰卧位和对重力挑战的反应中,pSS患者观察到更强的交感神经活动。我们假设这种增强的交感神经血管收缩活动可能反映了在血管反应性可能降低的情况下维持血压的一种尝试。