Effects of electrostimulation and administration of succinylcholine on the expression of Fos protein in mesencephalic periaqueductal gray matter of rats after simulated weightlessness

BACKGROUND： Expression of Fos in neurons of periaqueductal gray （PAG） is used to reflect the excitability. However, changes of expression of Fos in neurons of PAG are caused by injured electrostimulation after simulated weightlessness, and the relationship between pretreatment and injection of succinylcholine has not been determined yet. OBJECTIVE ： To investigate the changes of expression of Fos in PAG induced by injured electrostimulation pretreatment and injection of succinylcholine at 2 weeks after simulated weightlessness.DESIGN： Observational and controlled animal study.SETTING： Department of Physiology, Medical School, Xi＇an Jiaotong University; Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education. MATERIALS： A total of 24 adult female SD rats, of clean grade and weighing 180-220 g, were selected in this study. METHODS： The experiment was completed in the Experimental Animal Center of Xi＇an Jiaotong University.① All rats were randomly divided into 2 groups according to body mass： simulated weightlessness group and control group with 12 in each group. And then, each group was also divided into 3 subgroups： electrostimulation group, succinylcholine-pretreatment group and succinylcholine-injection group with 4 in each subgroup. ②The model of weightlessness was simulated by tail-suspended female rats, which were described and modified by Cheng Jie. Rats in normal control group were given the same interventions as simulated weightlessness group except for tail-suspended. ③ Experimental method： The rats in electrostimulation group were given nociceptive stimulus by a pair of subcutaneous electrodes inserted into 1 and 5 claw of left hindlimb. The stimulus （current： 10 mA; duration： 1 ms; interval： 1 s） lasted for 30 minutes. The rats in succinylcholine-pretreatment group received stimulus after intravenous administration of succinylcholine, rats in succinylcholine-injection group were not given stimulus, just received succinylcholine. ④ All rats were perfused and fixed after 2 hours from the end of stimulation. The brains were removed, and serial frozen sections of midbrain were stained using immunocytochemical method, observed and taken photos under light-microscope. The number and morphological characters of Fos-immunoreactive （Fos-IR） neurons in ventrolateral part of PAG were investigated. MAIN OUTCOME MEASURES： The alterations in number and morphological characters of Fos-IR neurons in ventrolateral PAG of all rats.RESULTS： A total of 24 rats were involved in the final analysis. ① The morphological changes of Fos-IR neurons： The expressions of Fos in ventrolateral part of PAG were observed in both control and simulated weightlessness groups rats after being given nociceptive stimulus. As compared with control group, Fos-IR neurons in simulated weightlessness group were dyed lightly, cellular integrity was impaired, and cellular verge was unclear. ② The numbers of Fos-IR neurons： In control group, the numbers of Fos-IR neurons in ventrolateral part of PAG in simulated weightlessness group were obviously lower than succinylcholine-pretreatment group, but obviously higher than succinylcholine-injection group （46.94±3.38, 71.06±8.96 and 35.04±4.62, respectively, P 〈 0.05）. In 14-day simulated weightlessness group, the numbers of Fos-IR neurons in electrostimulation group were also obviously lower than succinylcholine-pretreatment group, and obviously higher than succinylcholine-injection group （27.77±3.27, 32.91±2.99 and 11.75±1.00, respectively, P 〈 0.05）. The numbers of Fos-IR neurons in all subgroups in control group were obviously higher than those subgroups in simulated weightlessness group. Compared with electrostimulation group, the percentage of expression of Fos in ventrolateral part of PAG responsed to nociceptive stimulus after administration of succinylcholine （SCH） was increased to 51.83% in control group and 18.51% in simulated weightlessness group.CONCLUSION ：① The expression of Fos in neurons in ventrolateral part of PAG were increased by the pretreatment of SCH before nociceptive stimulus.② Nociceptive stimulus could increase the expression of Fos in neurons in ventrolateral part of PAG. ③ The numbers of Fos-IR neurons in ventrolateral part of PAG were decreased obviously after 2-week simulated weightlessness.

INFLUENCE OF SUCCINYLCHOLINE ON THE DOSE-RESPONSE RELATIONSHIP OF SUBSEQUENTLY ADMINISTERED ROCURONIUN

Objective To investigate the effect of succinylcholine on the dose-response relationship of sub-sequently administered rocuronium in healthy patients. Methods Forty-eight ASA physical status I-II patients,aged 17-65 years, scheduled for elective general surgery, were randomly assigned to either the rocuronium treat-ment group (R) or succinylcholine-rocuronium treatment group (SR). General anesthesia was induced with thio-pental 4 to 6mg/kg and fentanyl 2 to 5/μg/kg intravenously and maintained with 60% nitrous oxide in oxygen. Addi-tional doses of thiopental or fentanyl were administered as required. The dose-response relationship of rocuroniumwas determined by the single dose-response technique. In R group (n =24) , rocuronium was given after induction ofanesthesia. In SR group (n =24) , patients were intubated after 1. 5mg/kg of succinylcholine and rocuronium wasgiven after the complete recovery of neuromuscular blockade from succinylcholine. Patients were further randomlydivided into 4 subgroups receiving 150, 200, 250 or 300μg/kg of rocuronium respectively in both groups. Neuro-muscular function was assessed accelographically with train-of-four (TOF) stimulation at the wrist every 12s (usingthe TOF Guard? accelerometer). The relationship between probit-tranformed percentage depression of first twitchheight (Th) of train-of-four stimulation and logarithm dose of rocuronium was analyzed using linear regression.Results The dose-response curve of rocuronium after succinylcholine was shifted to the left in a parallel fashioncompared with that of rocuronium given alone. ED50 and ED95 of rocuronium were 193 ± 69 and 367 ± 73μg/kg re-spectively in R group, and 158 ±35 and 317 ±80μg/kg respectively in SR group (P <0.05). Conclusion Suc-cinylcholine shifts the dose-response curve of rocuronium to the left and potentiates the effects of the neuromuscularblockade by about 15% of subsequently administered rocuronium. Lower doses of rocuronium are required afterprior succinylcholine.

THE ROLE OF BRAIN-STEM DISCENDING INHIBITORY SYSTEM IN THE ANTINOCICEPTIVE EFFECT ELICITED BY MUSCLE SPINDLE AFFERENTS

Objective To analyse the antinociceptive effect of muscle spindle afferents and the involved mechanism.Methods The single unit of wide dynamic range neurons in the spinal cord dorsal horn were recorded extracelluarly.The effects of muscle spindle afferents elicited by intravenous administration of succinylcholine on nociceptive responses (C fibres evoked responses,C responses) of WDR neurons were observed before and after bilateral lesions of ventrolateral periaqueduct gray .And the effects of muscle spindle afferents on the spontaneous discharge of the tail flick related cell in the rostral ventro medial medulla and on the spontaneous discharge of the PAG neurons were observed.Results The C responses of WDR neurons were significantly inhibited by muscle spindle afferents,and the inhibitory effects were reduced by bilateral lesions of ventrolateral PAG.The spontaneous discharge of the off cell in the RVM was excited while the on cell was inhibited by intravenous administration of Sch.The spontaneous discharge of the PAG neurons were excited by muscle spindle afferents.Conclusion Muscle spindle afferents show a distinct effect of antinociception.PAG RVM descending inhibitory system may play an important role in this nociceptive modulative mechanism.

THE ROLE OF NUCLEUS RAPHE MAGNUS IN THE ANTINOCICEPTIVE EFFECT OF MUSCLE SPINDLE AFFERENTS IN THE RAT

Objective To investigate the role of NRM in the antinociceptive effect of muscle spindle afferents,the influence of NRM lesion on the inhibitory effect of muscle spindle afferents on the nociceptive responses of wide dynamic range (WDR) neurons and the effects of the muscle spindle afferents on the NRM neuronal activities were observed. Methods The single units of WDR neurons in the spinal dorsal horn were recorded extracellularly, and the inhibitory effects of activating muscle spindle afferents by intravenous administration of succinylcholine (SCH) on the C fibers evoked responses (C responses) of WDR neurons were tested before and after lesion of NRM.The effects of the muscle spindle afferents activated by administrating SCH on the single NRM neurons were also examined.Results ①It was found that the C responses of WDR neurons were significantly inhibited by intravenously administration of SCH, and the inhibitory effect was reduced after lesion of NRM;②The activities of most of the NRM neurons could be changed significantly by administrating SCH. According to their responses, NRM neurons could be classified into three types:excitatory, inhibitory and non responsive neurons, and the responses were dose dependent. Conclusion These results suggest that the muscle spindle afferents evoked by SCH may activate the NRM neurons, which plays an important role in the antinociception of muscle spindle afferents.

Pseudocholinesterase Deficiency: A Case Report and Literature Review

A 72-year-old male underwent neck dissection and parotidectomy with facial nerve preservation. Endotracheal intubation was facilitated with succinylcholine. Prolonged muscle paralysis which was first detected after failure to stimulate the facial nerve with electrocautery, lasted five hours. Laboratory tests indicated pseudocholinesterase (PChE) deficiency. A thyroidectomy one month later was performed uneventfully using rocuronium as a muscle relaxant. Literature review revealed a total of 40 PChE deficiency cases being reported since 1956.

Selection of neuromuscular blocking agents in patients undergoing renal transplantation under general anesthesia

OBJECTIVE: To study the pharmacodynamics of vecuronium,atracurium, mivacurium and rocuronium in patients with end-stage renal failure. METHODS: Forty-six patients with end-stage renal failure scheduled for renal transplantation and 53 patients with normal renal function were given either vecuronium, atracurium, mivacurium or rocuronium. The neuromuscular effects were monitored by the evoked response of the adductor pollicis to train-of-four stimulation of the ulnar nerve. RESULTS: Onset of vecuronium, atracurium and mivacurium occurred faster or tended to be faster in patients with end-stage renal failure, but there was no significant difference in onset by rocuronium between the control patients and renal failure patients. Furthermore, the no-response period, duration of action and recovery of atracurium did not differ between the two groups. There was no significant difference in duration of action or recovery of mivacurium between the two groups, whereas its no-response period was significantly prolonged in the patients with end-stage renal failure. There was no difference in no-response period or duration of action after the initial dose of vecuronium or rocuronium between the two groups. However, no-response period and duration of effect by vecuronium and rocuronium were prolonged with increasing incremental doses in patients with end-stage renal failure. CONCLUSIONS: All four muscle relaxants could be safely used in patients with end-stage renal failure. Onset of the relaxants were, in some cases, accelerated and no-response period of mivacurium was prolonged in patients with end-stage renal failure undergoing dialysis therapy. End-stage renal failure prolonged the no-response period and duration of action of vecuronium and rocuronium after repeated incremental doses, but did not alter those attributed to atracurium.