Wu Maddalena A, Casella Francesco, Perego Francesca, Suffritti Chiara, Afifi Afifi Nada, Tobaldini Eleonora, Zanichelli Andrea, Cogliati Chiara, Montano Nicola, Cicardi Marco
Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy.
Department of Clinical Sciences and Community Health, IRCCS Ca' Granda Foundation, Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
PLoS One. 2017 Nov 6;12(11):e0187110. doi: 10.1371/journal.pone.0187110. eCollection 2017.
Attacks of Hereditary Angioedema due to C1-inhibitor deficiency (C1-INH-HAE)are often triggered by stressful events/hormonal changes.
Our study evaluates the relationship between autonomic nervous system (ANS) and contact/complement system activation.
Twenty-three HAE patients (6 males, mean age 47.5±11.4 years) during remission and 24 healthy controls (8 males, mean age 45.3±10.6 years) were studied. ECG, beat-by-beat blood pressure, respiratory activity were continuously recorded during rest (10') and 75-degrees-head-up tilt (10'). C1-INH, C4, cleaved high molecular weight kininogen (cHK) were assessed; in 16 patients and 11 controls plasma catecholamines were also evaluated. Spectral analysis of heart rate variability allowed extraction of low-(LF) and high-(HF) frequency components, markers of sympathetic and vagal modulation respectively.
HAE patients showed higher mean systolic arterial pressure (SAP) than controls during both rest and tilt. Tilt induced a significant increase in SAP and its variability only in controls. Although sympathetic modulation (LFnu) increased significantly with tilt in both groups, LF/HF ratio, index of sympathovagal balance, increased significantly only in controls. At rest HAE patients showed higher noradrenaline values (301.4±132.9 pg/ml vs 210.5±89.6pg/ml, p = 0.05). Moreover, in patients tilt was associated with a significant increase in cHK, marker of contact system activation (49.5 ± 7.5% after T vs 47.1 ± 7.8% at R, p = 0.01).
Our data are consistent with altered ANS modulation in HAE patients, i.e. increased sympathetic activation at rest and blunted response to orthostatic challenge. Tilt test-induced increased HK cleavage suggests a link between stress and bradykinin production.
由于C1抑制物缺乏导致的遗传性血管性水肿（C1-INH-HAE）发作常由应激事件/激素变化引发。
我们的研究评估自主神经系统（ANS）与接触/补体系统激活之间的关系。
研究了23例缓解期的HAE患者（6例男性，平均年龄47.5±11.4岁）和24例健康对照者（8例男性，平均年龄45.3±10.6岁）。在静息状态（10分钟）和75度头高位倾斜（10分钟）期间持续记录心电图、逐搏血压、呼吸活动。评估C1-INH、C4、裂解的高分子量激肽原（cHK）；在16例患者和11例对照者中还评估了血浆儿茶酚胺。心率变异性的频谱分析可分别提取低频（LF）和高频（HF）成分，分别是交感神经和迷走神经调节的标志物。
HAE患者在静息和倾斜状态下的平均收缩压（SAP）均高于对照者。倾斜仅在对照者中引起SAP及其变异性显著增加。尽管两组中交感神经调节（LFnu）随倾斜均显著增加，但交感迷走平衡指数LF/HF比值仅在对照者中显著增加。静息时HAE患者的去甲肾上腺素值较高（301.4±132.9 pg/ml对210.5±89.6 pg/ml，p = 0.05）。此外，在患者中，倾斜与接触系统激活标志物cHK的显著增加相关（倾斜后为49.5±7.5%，静息时为47.1±7.8%，p = 0.01）。
我们的数据与HAE患者ANS调节改变一致，即静息时交感神经激活增加，对直立性挑战的反应减弱。倾斜试验诱导的HK裂解增加提示应激与缓激肽产生之间存在联系。
