Local sympathetic function in human skeletal muscle and adipose tissue assessed by microdialysis

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.