Lambert G W, Kaye D M, Vaz M, Cox H S, Turner A G, Jennings G L, Esler M D
Human Autonomic Function Laboratory, Baker Medical Research Institute, Prahran, Victoria, Australia.
J Auton Nerv Syst. 1995 Nov 6;55(3):169-78. doi: 10.1016/0165-1838(95)00041-u.
The plasma level and urinary excretion of 3-methoxy-4-hydroxyphenylglycol (MHPG), the principal metabolite of noradrenaline in the brain, are often used as indicators of central nervous system noradrenergic activity. Using percutaneously placed catheters, we studied the regional inputs into the plasma MHPG pool in 62 healthy volunteers. Veno-arterial plasma concentration differences and regional organ blood flows were used to quantify the relative amounts of MHPG contributed by various sites into plasma. Positive veno-arterial concentration gradients were found across the forearm, cardiac and jugular vessels in the healthy subjects. By far the majority of MHPG in plasma was derived from skeletal muscle, 5.3 +/- 1.8 nmol/min, with only minimal contribution (0.9 +/- 0.2 nmol/min) from the brain. Thus, to obtain an accurate indication of central nervous system noradrenergic activity the confounding influences of regional MHPG production must be excluded. 34 patients with chronic congestive heart failure, 6 patients with pure autonomic failure and 9 recent heart transplant recipients were used to investigate the possible effects of chronic sympathetic nervous system overactivity and sympathetic underactivity and denervation on peripheral MHPG production and plasma MHPG concentration. To examine the utility of plasma MHPG determinations as an indicator of acute alterations in sympathetic nervous activity we examined the influence of a variety of laboratory stressors on the arterial level and cardiac production of MHPG. The resting arterial plasma MHPG concentration mirrored sympathetic function in the patients with cardiac failure (sympathetic activation) and pure autonomic failure (sympathetic denervation), with mean MHPG plasma concentrations being 180 and 40% of those in healthy subjects. Cardiac MHPG production was increased in heart failure patients, and near zero with the cardiac sympathetic denervation accompanying transplantation and pure autonomic failure. In contrast, acute reflex stimulation of sympathetic nervous activity was not associated with parallel changes in the arterial level or cardiac production of MHPG. Measurements of peripheral plasma MHPG levels provide an index of prevailing sympathetic nervous function in clinical models of sympathetic overactivity and denervation, but are insensitive to acute sympathetic nervous system responses.
3-甲氧基-4-羟基苯乙二醇（MHPG）是脑中去甲肾上腺素的主要代谢产物，其血浆水平和尿排泄量常被用作中枢神经系统去甲肾上腺素能活性的指标。我们使用经皮放置的导管，研究了62名健康志愿者血浆MHPG库的区域输入情况。利用静脉-动脉血浆浓度差异和区域器官血流量来量化不同部位对血浆中MHPG的相对贡献量。在健康受试者中，在前臂、心脏和颈静脉血管处发现了正向的静脉-动脉浓度梯度。血浆中绝大多数的MHPG来自骨骼肌，为5.3±1.8纳摩尔/分钟，而脑的贡献极小（0.9±0.2纳摩尔/分钟）。因此，为了准确指示中枢神经系统去甲肾上腺素能活性，必须排除区域MHPG产生的混杂影响。34例慢性充血性心力衰竭患者、6例单纯自主神经功能衰竭患者和9例近期心脏移植受者被用于研究慢性交感神经系统活动亢进、交感神经活动减退和去神经支配对周围MHPG产生及血浆MHPG浓度的可能影响。为了检验血浆MHPG测定作为交感神经活动急性改变指标的实用性，我们研究了多种实验室应激源对动脉水平及心脏产生MHPG的影响。静息时动脉血浆MHPG浓度反映了心力衰竭患者（交感神经激活）和单纯自主神经功能衰竭患者（交感神经去神经支配）的交感神经功能，其平均血浆MHPG浓度分别为健康受试者的180%和40%。心力衰竭患者心脏MHPG的产生增加，而在移植伴心脏交感神经去神经支配及单纯自主神经功能衰竭时，心脏MHPG产生接近零。相比之下，交感神经活动的急性反射性刺激与动脉水平或心脏MHPG产生的平行变化无关。外周血浆MHPG水平的测量为交感神经活动亢进和去神经支配的临床模型中占主导地位的交感神经功能提供了一个指标，但对交感神经系统的急性反应不敏感。
