Effects of 5-hydroxytryptamine on Rocuronium-induced Neuromuscular Blockade in a Rat Phrenic Nerve-hemidiaphragm Preparation

Abstract

Background: The 5-hydroxytryptamine 3 receptor (5-HT3R) is a member of a superfamily of ligand-gated ion channels which has structural similarities and common evolutionary origin to those of the nicotinic acetylcholine receptor (nAChR). 5-hydroxytryptamine (5-HT) and muscle relaxants may have cross reaction. Rocuronium is a non-depolarizing neuromuscular blocking agent which has a rapid onset. The aim of this study was to examined the effects of 5-HT on rocuronium-induced neuromuscular blockade in a rat phrenic nerve-hemidiaphragm preparation. Methods: Institutional approval was obtained for the experimental procedure. Fifty male Sprague-Dawley rats (150－200 g) were divided into 5 groups; the control, and 0.1, 1, 10, and 20μg/ml of 5-HT. The animals were injected with phentobarbital at 40 mg/kg into the peritoneal cavity. The hemidiaphragm with the phrenic nerve was dissected and then mounted in a bath containing 100 ml Krebs solution at room temperature. The phrenic nerve was stimulated at the supramaximal intensity using a Grass® S88 stimulator via an SIU5 isolation unit. The twitch height was measured and recorded using a precalibrated Grass® FT88 force displacement transducer and recorded with a Grass® 79 polygraph, respectively. In the cumulative dose-response study, the rocuronium 100μg/dl and each dose of 5-HT were administered simultaneously administered, with additional 50μg/dl incremental doses of rocuronium were added to obtain grteater than 95% neuromuscular twitch inhibition. The ED5, ED50, ED90, and ED95 of rocuronium in each group were calculated using a probit model. Results: The ED50, ED90, and ED95 of rocuronium were significantly reduced in 5-HT 20μg/ml group (P ＜ 0.05), but no differences were observed with the other 5-HT groups compared to the control groups. Conclusions: 5-HT at 20μg/ml enhanced the neuromuscular blockade of rocuronium.