EPIDURAL CLONIDINE DEPRESSES SYMPATHETIC-NERVE ACTIVITY IN HUMANS BY A SUPRASPINAL MECHANISM

Background. Epidural administration of the alpha2-adrenergic agonist c lonidine induces hypotension. Animal experiments have indicated a poss ible spinal mechanism through activation of alpha2-adrenergic receptor s on sympathetic preganglionic neurons, resulting in a decrease of eff erent sympathetic activity. However, the pharmacokinetic behavior of e pidural clonidine, the high lipid solubility of the drug, and the appa rent sedative side effects also indicate a possible supraspinal mechan ism. To test this hypothesis, the effect of epidural and intramuscular clonidine on efferent sympathetic nerve activity to the leg was studi ed with microneurography. Methods. In 15 healthy volunteers, a lumbar epidural catheter was inserted and multiunit postganglionic sympatheti c activity was recorded in a skin or muscle fascicle of the peroneal n erve before and after epidural injection of clonidine. Skin blood flow in the hand and in the foot was measured with laser Doppler flowmetry . In six additional experiments, performed at another time, clonidine was given intramuscularly. Results. After epidural injection of clonid ine (3 mug/kg) the resting level of skin sympathetic activity decrease d to 18 +/- 5% (n = 6; P < 0.001), muscle sympathetic activity express ed as bursts/min to 41 +/- 12% (n = 7; P < 0.01), and integrated muscl e sympathetic activity to 41 +/- 13% (n - 7; P < 0.01) of control valu es after 30 min. However, the capacity for activation of skin sympathe tic activity by arousal stimuli and of muscle sympathetic activity by apnea remained. Intramuscular clonidine inhibited both skin sympatheti c activity (n = 3) and muscle sympathetic activity (n = 3) to the same extent. Skin blood flow increased whereas blood pressure and heart ra te decreased after epidural and intramuscular clonidine. Conclusions. The comparable inhibition of resting sympathetic nerve activity, paral leled by a decrease in heart rate and blood pressure after both epidur al and intramuscular clonidine, indicates that epidural clonidine indu ces a supraspinally evoked general decrease in sympathetic outflow.