EFFECTS OF INTRATHECAL NEOSTIGMINE, BUPIVACAINE, AND THEIR COMBINATION ON SYMPATHETIC-NERVE ACTIVITY IN RATS

Background: Intrathecal injection of local anesthetic agents is associ ated frequently with hypotension. Conversely, intrathecal administrati on of neostigmine increases blood pressure by enhancing the accumulati on of acetylcholine in the spinal cord. The current study examined dir ectly the interaction of intrathecal injection of bupivacaine and neos tigmine on splanchnic sympathetic efferent nerve activity. Methods: Ex periments mere performed in rats with intrathecal catheters implanted for the long-term. Rats were anesthetized with ketamine (40 mg/kg, int ramuscularly) and alpha-chloralose (60 mg/kg, intraperitoneally). The skin incision sites were infiltrated with 1% lidocaine. Sympathetic ef ferent activity was recorded from the left greater splanchnic nerve. S ympathetic nerve activity was measured continuously before and after i ntrathecal injection of saline, 430 nmol (140 mu g) of bupivacaine, 25 nmol (7.6 mu g) of neostigmine, and a combination of bupivacaine and neostigmine all in volumes of 5 mu l. Each group consisted of six anim als. Results: Compared with baseline nerve activity, intrathecal injec tion of neostigmine increased splanchnic sympathetic nerve activity si gnificantly by (mean +/- SEM) 112 +/- 29% after an onset latency of 6. 8 +/- 0.9 min. In contrast, bupivacaine decreased splanchnic nerve act ivity significantly (-65 +/- 13%) after a latency of 3.3 +/- 0.5 min a fter intrathecal administration. Similar to the effect of saline, intr athecal coadministration of bupivacaine and neostigmine did not alter the splanchnic sympathetic nerve activity significantly. Conclusions: The current study provides electrophysiologic evidence that intratheca l injection of neostigmine increases whereas bupivacaine decreases sym pathetic nerve activity. Further, addition of neostigmine effectively counteracts the inhibitory effect of spinal bupivacaine on the sympath etic nerve activity.