Human Neurotransmitter Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
Circ Arrhythm Electrophysiol. 2011 Oct;4(5):711-8. doi: 10.1161/CIRCEP.111.962332. Epub 2011 Aug 15.
The pathophysiology of vasovagal syncope is poorly understood, and the treatment usually ineffective. Our clinical experience is that patients with vasovagal syncope fall into 2 groups, based on their supine systolic blood pressure, which is either normal (>100 mm Hg) or low (70-100 mm Hg). We investigated neural circulatory control in these 2 phenotypes.
Sympathetic nervous testing was at 3 levels: electric, measuring sympathetic nerve firing (microneurography); neurochemical, quantifying norepinephrine spillover to plasma; and cellular, with Western blot analysis of sympathetic nerve proteins. Testing was done during head-up tilt (HUT), simulating the gravitational stress of standing, in 18 healthy control subjects and 36 patients with vasovagal syncope, 15 with the low blood pressure phenotype and 21 with normal blood pressure. Microneurography and norepinephrine spillover increased significantly during HUT in healthy subjects. The microneurography response during HUT was normal in normal blood pressure and accentuated in low blood pressure phenotype (P=0.05). Norepinephrine spillover response was paradoxically subnormal during HUT in both patient groups (P=0.001), who thus exhibited disjunction between nerve firing and neurotransmitter release; this lowered norepinephrine availability, impairing the neural circulatory response. Subnormal norepinephrine spillover in low blood pressure phenotype was linked to low tyrosine hydroxylase (43.7% normal, P=0.001), rate-limiting in norepinephrine synthesis, and in normal blood pressure to increased levels of the norepinephrine transporter (135% normal, P=0.019), augmenting transmitter reuptake.
Patients with recurrent vasovagal syncope, when phenotyped into 2 clinical groups based on their supine blood pressure, show unique sympathetic nervous system abnormalities. It is predicted that future therapy targeting the specific mechanisms identified in the present report should translate into more effective treatment.
血管迷走性晕厥的病理生理学尚不清楚，治疗通常无效。我们的临床经验是，根据患者的仰卧位收缩压，将血管迷走性晕厥患者分为 2 组，其收缩压要么正常（＞100mmHg），要么低（70-100mmHg）。我们研究了这 2 种表型的神经循环控制。
交感神经测试分为 3 个水平：电，测量交感神经放电（微神经图）；神经化学，定量去甲肾上腺素向血浆溢出；细胞水平，通过交感神经蛋白的 Western blot 分析。在 18 名健康对照者和 36 名血管迷走性晕厥患者中进行了头高位倾斜（HUT）测试，模拟站立时的重力应激，其中 15 名患者为低血压表型，21 名患者为正常血压表型。健康受试者在 HUT 期间，微神经图和去甲肾上腺素溢出明显增加。正常血压表型的 HUT 期间微神经图反应正常，低血压表型则明显增强（P=0.05）。去甲肾上腺素溢出反应在两组患者中均异常降低（P=0.001），表明神经放电与神经递质释放之间存在脱节；这降低了去甲肾上腺素的可利用性，从而损害了神经循环反应。低血压表型中去甲肾上腺素溢出减少与酪氨酸羟化酶减少（正常的 43.7%，P=0.001）有关，后者是去甲肾上腺素合成的限速步骤，而在正常血压中与去甲肾上腺素转运体水平升高（正常的 135%，P=0.019）有关，增加了递质的再摄取。
根据仰卧位血压将复发性血管迷走性晕厥患者分为 2 个临床组，发现他们存在独特的交感神经系统异常。可以预测，针对本报告中确定的特定机制的未来治疗方法应该会转化为更有效的治疗方法。
