Intrathecal Endothelin-1 Reduced the MAC of Isoflurane in the Rat

Jeong, Chang Young; Im, Woong Mo; Yoon, Myung Ha; Han, Sang Do; Jeong, Sung Wook

Abstract

BACKGROUND: Recent evidences suggest that anesthetic action within the spinal cord is important in suppressing somatic responses to painful stimuli. Intrathecal endothelin-1 (ET-1) is known to have antinociceptive effect. The purpose of this experiment was to determine whether intrathecal ET-1 may influence the minimum alveolar concentration (MAC) of isoflurane in rats and access the role of the spinal cord as the sites of anesthetic action in blocking somatic responsiveness.
METHODS
In Sprague-Dawley rats fitted with an indwelling intrathecal catheter, we determined the MAC of isoflurane using a tail-clamp technique as a painful stimulus, combined with end-tidal anesthetic sampling. In experiment 1, the control MAC was determined and changes of control MAC were observed after intrathecal ET-1 (4x10-2 nmol, 4x10-3 nmol) administration. In experiment 2, we observed the effects of L or N type Ca++ channel blocker such as verapamil (50 g) or W-conotoxin (0.5 g) on the MAC after measurement of the control MAC. In experiment 3, after measurement of the control MAC, ET-1 (10-2 nmol) was administered intrathecally and the MAC was determined again. Next, intrathecal verapamil (50 g) or W-conotoxin (0.5 g) was injected. After that, the MAC was determined again.
RESULTS
In experiment 1, ET-1 decreased the MAC of isoflurane and its effect was sustained over 2 hours. In experiment 2, the MAC, determined following administration of verapamil or W-conotoxin, was not different from that of the control. In experiment 3, the MAC was decreased after ET-1 administration and then increased following injection of verapamil or W-conotoxin.
CONCLUSIONS
These results suggested that ET-1, in relation to calcium, might play an important role in determining the MAC of isoflurane in the spinal cord.