Bruce Simon, Tack Cees, Patel Jigisha, Pacak Karel, Goldstein David S
NINDS, NIH, Bethesda, Maryland 20892-1620, USA.
Clin Auton Res. 2002 Feb;12(1):13-9. doi: 10.1007/s102860200005.
In response to stressors and pathophysiologic conditions, sympathetic neuronal outflows can change heterogeneously among body organs and tissues. This study examined the validity of microdialysis and measurements of microdialysate concentrations of catechols, to assess local sympathetic function in skeletal muscle and adipose tissue in humans.
Based on preliminary experiments, a microdialysate perfusion rate of 3 microl/min and collection duration of 30 minutes were chosen. To assess responses to a stimulus that increases sympathetic outflow to skeletal muscle, microdialysate norepinephrine and dihydroxyphenylglycol concentrations in quadriceps muscle, abdominal subcutaneous adipose tissue, and plasma were measured during orthostasis in 8 healthy normal volunteers. To assess responses to decreased postganglionic sympathetic nerve traffic, norepinephrine and dihydroxyphenylglycol concentrations were measured during i. v. infusion of trimethaphan in 5 volunteers.
All subjects had detectable norepinephrine and dihydroxyphenylglycol in microdialysate from both skeletal muscle and adipose tissue. Orthostasis significantly increased microdialysate norepinephrine in skeletal muscle (0.38 +/- (SEM) 0.07 nmol/L supine to 1.48+/-0.24 nmol/L standing, p < 0.01) and in adipose tissue (0.31+/-0.02 nmol/L supine to 0.68+/-0.11 nmol/L standing, p < 0.01). Orthostasis also increased microdialysate dihydroxyphenylglycol in both tissues (1.76+/-0.30 nmol/L to 3.08+/-0.43 nmol/L, p < 0.01; 1.37+/-0.15 nmol/L supine to 1.99+/-0.34 nmol/L standing, p < 0.01). Trimethaphan decreased norepinephrine concentrations in skeletal muscle microdialysate by 50%, adipose tissue by 70%, and antecubital venous plasma 50%, with non-significant decreases in dihydroxyphenylglycol concentrations at each site.
Microdialysate concentrations of norepinephrine and dihydroxyphenylglycol can be detected reliably and respond appropriately during manipulations that increase or decrease the sympathetically mediated release and turnover of norepinephrine. This approach may provide a means to assess sympathetic neuronal function in skeletal muscle and adipose tissue in humans with known or suspected dysautonomias.
为应对应激源和病理生理状况，交感神经神经元的传出在身体各器官和组织之间会发生异质性变化。本研究检验了微透析及儿茶酚类微透析液浓度测量在评估人体骨骼肌和脂肪组织局部交感神经功能方面的有效性。
基于初步实验，选择了3微升/分钟的微透析液灌注速率和30分钟的采集时长。为评估对增加骨骼肌交感神经传出刺激的反应，在8名健康正常志愿者立位期间，测量了股四头肌、腹部皮下脂肪组织和血浆中的微透析液去甲肾上腺素和二羟苯乙二醇浓度。为评估对节后交感神经活动减少的反应，在5名志愿者静脉输注三甲噻芬期间，测量了去甲肾上腺素和二羟苯乙二醇浓度。
所有受试者骨骼肌和脂肪组织的微透析液中均可检测到去甲肾上腺素和二羟苯乙二醇。立位显著增加了骨骼肌微透析液中的去甲肾上腺素（仰卧位时为0.38±（标准误）0.07纳摩尔/升，站立位时为1.48±0.24纳摩尔/升，p<0.01）和脂肪组织中的去甲肾上腺素（仰卧位时为0.31±0.02纳摩尔/升，站立位时为0.68±0.11纳摩尔/升，p<0.01）。立位还增加了两个组织中的微透析液二羟苯乙二醇（1.76±0.30纳摩尔/升增至3.08±0.43纳摩尔/升，p<0.01；仰卧位时为1.37±0.15纳摩尔/升，站立位时为1.99±0.34纳摩尔/升，p<0.01）。三甲噻芬使骨骼肌微透析液中的去甲肾上腺素浓度降低了50%，脂肪组织降低了70%，肘前静脉血浆降低了50%，各部位二羟苯乙二醇浓度的降低无统计学意义。
去甲肾上腺素和二羟苯乙二醇的微透析液浓度能够被可靠检测，且在增加或减少去甲肾上腺素交感介导的释放和周转的操作过程中会有相应反应。这种方法可能为评估已知或疑似自主神经功能障碍患者的骨骼肌和脂肪组织中的交感神经功能提供一种手段。
