INTERACTION BETWEEN BETAMETHASONE AND VECURONIUM

A possible interaction between betamethasone and vecuroniumwas examined in 20 rat phrenic nerve-hemidiaphragm preparations.Ten preparations were bathed in a physiological solution withbetamethasone 1 µmol litre^–1 added and, after a30-min period were exposed to vecuronium at concentrations of4, 6, 8 and 10 nmol litre^–1 with vecuronium free washingsbetween each exposure. Ten control experiments were performedalso using a betamethasone-free bathing solution. In comparisonwith control, the betamethasone group had significantly (P =0.0008) less depression of muscle contraction (twitch) forceat all concentrations of vecuronium. The calculated EDX (50%depression of muscle contraction force) was 5.65 µmollitre^–1 for controls and 7.39 µmol litre^–1for betamethasone- pretreated preparations. This study confirmsour previous clinical observations that an interaction occursbetween vecuronium and betamethasone which is characterizedby resistance to neuromuscular block.     

INTERACTION BETWEEN PANCURONIUM BROMIDE AND VECURONIUM BROMIDE

The interaction between two non-depolarizing neuromuscular blockingagents, pancuronium bromide and vecuronium bromide, has beenstudied at standardized levels of neuromuscular blockade andalternating the sequence of their administration, in 40 surgicalpatients. The drug administered first appeared invariably toplay a dominant role in influencing both the dose requirementsand the duration of action of the subsequent neuromuscular blocker.This resulted in reduced dose requirements and significant prolongationof action of vecuronium administered after pancuronium and increaseddose requirements and shortening of neuromuscular blocking actionof pancuronium given during vecuronium-induced partial neuromuscularblockade. Possible mechanisms of such interaction are discussed.     

COMPARISON BETWEEN THE CONTINUOUS INFUSION OF VECURONIUM AND THE INTERMITTENT ADMINISTRATION OF PANCURONIUM AND VECURONIUM

The neuromuscular blocking effects of repeated bolus injectionsof pancuronium, or vecuronium, and of the continuous infusionof vecuronium have been compared in 36 patients by means ofevoked twitch tension Groups I and II received a loading dose(0.075 mg kg^–1) of pancuronium or vecuronium, respectively,followed by 0.015-mg kg^–1 maintenance doses when twitchtension had recovered to 25%. Group III received a 0.075-mgkg^–1 loading dose of vecuronium plus a continuous infusion(commenced simultaneously) delivering 0.075 mg kg^–1 h^–1.With repeated injections of pancuronium (group I) or vecuronium(group II), the durations of blockade to 25% recovery were 64and 25 min, respectively. Maintenance doses had to be injectedevery 42 min with pancuronium and every 12 min with vecuronium.The recovery times from 25% to 75% of control twitch tensionwere 44 v. 12 min. The continuous infusion of vecuronium (groupIII) produced consistent neuromuscular blockade at an averagelevel of 87% twitch depression. The times from the end of infusionto 25%, and from 25% to 75%, recovery averaged 20 and 26 min,respectively. These values did not correlate with the totaldose of vecuronium infused. For clinical practice, the suggestedloading dose is 1.5 times the ED₉₀ (= 0.07 mg kg^–1) followedby an infusion of the same dose per hour. The infusion shouldbe started within 10 min of the injection of the loading dose.     

DOSE-RESPONSE RELATIONSHIPS AND NEUROMUSCULAR BLOCKING EFFECTS OF VECURONIUM AND PANCURONIUM DURING KETAMINE ANAESTHESIA

The dose-response curves of vecuronium and pancuronium werecompared during ketamine anaesthesia in 60 patients (ASA I).The relationship between the probit transformed depression oftwitch height and the logarithm of the dose was analysed by1ink regression. Vecuronium was found to be 1.2 times more potentthan pancuronium. ED₅₀ of vecuronium and pancuronium were 30.5µg kg^–1 and 37.0 µg kg^–1, and the ED₉₅45.6 µg kg^–1 and 59.5 µg kg^–1, respectively.Using equipment doses of vecuronium and pancuronium (1.6ED₉₅)indices of neuromuscular blockade were compared in a further20 patients (ASAI). No statistically signifimnt difference wasfound in onset time. The duration of action following vecuroniumwas significantly shorter than after pancuronium. The time to25% recovery of twitch height following vecuronium 73 µgkg^–1 was 22.2 min compared with 66.6 min following pancuronium99 µg kg^–1. Following supplementary doses of vecuronium,a statistically significant increase in duration of action wasseen following the fourth and fifth doses. Reversal timr ofvecuronium to a train-of-four ratio of 0.7 was significantlyshorter than that of pancuronium (8.3 min and 13.6 min, respectively)     

INTERACTION OF CYCLOSPORIN AND ITS SOLVENT, CREMOPHOR, WITH ATRACURIUM AND VECURONIUM

Interactions between Sandimmun (formulated as cyclosporin (CyA)in Cremophor and ethanol) and atracurium or vecuronium wereinvestigated inanaesthetizedcats. Duringstable50% blockade andwith a constant rate of infusion of the neuromuscular blockingdrugs, Sandimmun 0.8 mg kg^–1 or an equivalent amount ofits solvent moiety was injected over 5 min. Sandimmun potentiatedthe blockade induced by vecuronium (median infusion rate 110µg kg^–1 h^–1) from 50.7% before injection tomaximum 95.2% 17.3 min after injection (median values), whereasthe median blockade in cats receiving atracurium (median 250pig kg^–1 h^–1) increased from 51.3% to 72.4% after32.9 min. At 45 min after the injection the median blockadeswere 93.1% and 69.8%, respectively. In cats receiving vecuronium(median 104 µg kg^–1 h^–1) the solvent producedan increase in effect of from 51.1% to maximum 78.0% blockadeafter 5.4min and 61.5% after 45 min (median values). Interactionwith solvent was negligible in cats receiving atracurium. Weattribute the effect of the solvent to the Cremophor component.The mechanism of the interaction related to the cyclosporinis unknown. ^*Present address: Apothekernes Laboratorium A. S, Harbnitzalleen3, N-0275 Oslo 2, Norway.     

SYNERGISM BETWEEN ATRACURIUM AND VECURONIUM IN CHILDREN

In 30 children under balanced anaesthesia, we have determineddose-response curves and maintenance requirement of three doseratio combinations of atracurium and vecuronium (10: 1, 4:1or 1.6: 1 on a µg:µg. basis). Neuromuscular blockwas monitored by adductor poiicis EMG. An equipotent dose ratio(4:1) was most potent, with a mean (SEM) ED₉₅ of atracurium95 (6) µg kg^–1 with vecuronium 24 (1) µg kg^–1The sum of these doses is only 58% of an ED₉₅ value of one agent(P = 0.000 1). The hourly requirement to maintain a 90–95%neuromuscular block was 2.0 (0.1) times an individual ED₉₅ doseof any combination. Recovery index was 8.9 (0.5) min. Theseresults indicate that a combination of atracurium and vecuroniumis supra-additive compared with the effects of each drug alone.However, all combinations maintained an intermediate characterof neuromuscular block. Combining atracurium with vecuroniummay reduce drug requirement by 40%. (Br. J. Anaesth. 1993; 71:440–442)     

EFFECTS OF PIPECURONIUM AND PANCURONIUM ON THE ISOLATED RABBIT HEART

We have studied the effects of pipecuronium and pancuroniumon myocardial contractility and heart rate in two differentanimal preparations. Pipecuronium and pancuronium produced nochange in isometric contraction of rabbit atria. The chronotropiceffects of pipecuronium, pancuronium and vecuronium were investigatedusing acetylcholine as an agonist in isolated perfused rabbitheart. Pancuronium but not pipecuronium or vecuronium, produceda significant degree of antagonism to the bradycardia producedby acetylcholine.     

成骨细胞与生物衍生支架材料相互作用的基因表达研究

目的研究组织工程骨体外构建过程中,成骨细胞与生物衍生骨相互作用的基因表达。方法用人胚骨膜来源的成骨细胞与生物衍生骨体外复合培养构建组织工程骨。培养2、4、6、8和10d,分别提取总RNA,经逆转录成cDNA。用荧光及TaqMan探针行实时定量PCR,分别扩增成骨细胞特异转录因子(Cbfa1)、成骨细胞特异基因(Osterix)、型胶原、骨钙素(osteocalcin,OC)和整合素α5和β1(Integrinα5andβ1),读取扩增循环数(Ct值),进行统计学分析。以单纯培养的成骨细胞作为对照组。结果Cbfa1与Osterix变化一致,其中实验组Osterix在2d和8d的表达均明显高于对照组(P<0.05)。型胶原与OC的表达变化一致,实验组除10d时,其余各时间段型胶原表达均明显低于对照组(P<0.01)。Intgerin的表达始终处于较高水平,在培养最初的2d,实验组Integrinβ1表达明显高于对照组(P<0.01)。结论成骨细胞与生物衍生材料复合后,重要基因可持续正常表达。作为支架材料,生物衍生骨在保持成骨细胞性状、诱导及促进成骨细胞分化方面有明显优越性;它不仅对细胞顺利进入增殖状态无影响,而且为细胞增殖提供广阔而有效的空间。成骨细胞最终可良好分化,充分发挥成骨功能,并有利于成骨细胞黏附,黏附行为贯穿细胞与材料相互作用的整个过程,而并非局限于开始阶段。     

RELATIONSHIP BETWEEN POST-TETANIC TWITCH AND SINGLE TWITCH RESPONSE AFTER ADMINISTRATION OF VECURONIUM

We have studied the relationship between posttetanic twitch(PTT) and single twitch response after administration of vecuronium0.2 mg kg^–1 in 100 patients during neuroleptanaesthesia(NLA) (droperidol and fentanyl) and during anaesthesia withhalo thane, isoflurane, enflurane or sevoflurane (1 MAC in nitrousoxide and oxygen). Intervals from PTT₁ to single twitch, andpost-tetanic-count (PTC) (number of PTT responses) at the onsetof single twitch were determined electromyographically. Theseintervals in the isoflurane, enflur ane and sevoflurane groupsdiffered from those in NLA and halothane groups. PTC in theisoflurane, enflurane and sevoflurane groups differed from thosein the NLA group, and PTC in the sevoflurane group significantlyfrom those in the NLA and halothane groups. These results areconsistent with the view that PTT reflects prejunctional block,whilst the single twitch response is indicative of postjunctionalblock. (Br. J. Anaesth. 1993; 71: 443–444)     

STUDY OF THE POSSIBLE INTERACTION BETWEEN FENTANYL AND PROPOFOL USING A COMPUTER-CONTROLLED INFUSION OF PROPOFOL

A computer-controlled infusion of propofol designed to achievea target blood concentration of propofol 3 µg ml^–1was used to investigate the possibility of an interaction betweenpropofol and fentanyl in 32 patients undergoing body surfacesurgery. In 16 patients who were not receiving a neuromuscularblocker during maintenance anaesthesia with 67% nitrous oxide,there were no significant differences in blood concentrationsof propofol between eight patients who received fentanyl 5 µgkg^–1 before induction of anaesthesia, and eight patientswho did not. In a further 16 patients who received vecuroniumduring maintenance anaesthesia with 67% nitrous oxide, therewere no significant differences in blood propofol concentrationsbetween eight patients who received fentanyl 5 µg kg^–1before induction of anaesthesia, and eight patients who didnot. Fentanyl administered i.v. immediately before a computer-controlledinfusion of propofol resulted in more satisfactory anaestheticconditions than when fentanyl was not used, but did not significantlyprolong the recovery time.     

ATRACURIUM AND VECURONIUM: EFFECT OF DOSE ON THE TIME OF ONSET

The time intervals measured from the administrations of eitheratracurium or vecuronium to maximum or 95% neuromuscular blockade(T_max) were compared in 70 patients using the evoked compoundaction potential of the adductor pollicis muscle. Equipotentdoses, calculated from the relationship between dose and responsefor both drugs obtained in an earlier study, were compared.The doses of atracurium and vecuronium ranged from 0.135 to0.5 mg kg^–1 and from 0.02 to 0.1 mg kg^–1, respectively.The dose range for both drugs included the ED₅₀, ED₉₅ and thedose required to produce 100% blockade (ED_"100"). No significantchanges in mean T_max occurred for doses of atracurium in therange 0.135–0.2 mg kg^–1 and in the range 0.24–0.5mg kg^–1. Similarly, no change in T_max occurred at dosesof vecuronium in the range 0.02–0.05 mg kg^–1 and0.06–0.1 mg kg^–1. T_max, changed significantly inthe dose ranges atracurium 0.2–0.24 mg kg^–1 andVecuronium 0.05–0.06 mg kg^–1. There was no significantdifference in T_max when equipotent doses of atracurium and vecuroniumwere compared.     

肝内胆管癌与肝细胞癌免疫组化差异对比分析

目的统计、对比、分析肝内胆管癌（Intrahepatic Cholangiocarcinoma,ICC）及肝细胞癌（Hepatic Cell Carcinoma,HCC）免疫组化差异。方法术后病理诊断ICC患者810例作为研究组,随机抽取同期HCC患者810例作为对照组（肝门部胆管癌不在本次研究之列）;收集免疫组化资料用SPSS1 2．0软件统计,行χ^2检验或Fisher＇s检验。结果统计结果显示：ICC和HCC两组在Hep-1、HbsAg、CK19、CD34、P53、PCEA、CA19-9、HER-2、MUC1、CDIO、AQP-1有显著差异（P〈0．05）。结论ICC是原发性肝癌（Primary Liver Cancer,PLC）的一种特殊类型,其免疫组化特征与HCC有明显差异。     

INTERACTION BETWEEN HALOTHANE AND MU, DELTA AND KAPPA OPIOID AGONISTS ON THE ISOLATED RIGHT ATRIA OF THE RAT

We have examined the interaction between halo-thane and specificopioid agonists at mu (morphine and [D-ala² N-mephe⁴, gly-ol⁵J-enkephalin(DAGO)), delta ([D-pen^{2 5}]-enkephalin (DPDPE)) and kappa (trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolikynyl)cyclohexyl]-bencetamidemethanesul-phonate (U-50,488H))receptors on the isolated right atria of the rat. All the opioidagonists tested decreased atrial rate. The maximal effects obtainedwith U-50A88H (75 (SE 3.3)%) were significantly (P < 0.001)greater than those obtained with morphine (12(2.7)<), DAGO(8(0.6)<) or DPDPE (11 (1:8)<). Halothane 1.5 v/% didnot modify the inhibitory effects induced by morphine, DAGOor DPDPE. However, U-50,488H had a potentiating effect in thepresence of halothane 1.5 v/v% (P<0.001). Naloxone 5 x 1O^–7and 1 x 1O^–6 mol litre^–1 antagonized the inhibitoryeffects of U-50,488H in the presence of halothane. We concludethat halothane increased the potency of a kappa agonist on isolatedright atria and suggest that this effect was meded by opioidreceptors. (Br. J. Anaesth. 1992; 69:487–491)     

COMPARATIVE POTENCY OF PIPECURONIUM BROMIDE AND PANCURONIUM BROMIDE

Cumulative dose-response curves were constructed to determinethe comparative potency of pipecuronium and pancuronium. Fromthese, the ED₅₀ and ED₉₅ values were calculated. These were24.96 g kg^–1 and 44.96 µg kg^–1, respectively,for pipecuronium and 30.42 µg kg^–1 and 61.12 µgkg^–1, respectively, for pancuronium.     

RECOVERY OF ATRACURIUM AND VECURONIUM NEUROMUSCULAR BLOCK IN THE ISOLATED FOREARM

The duration of recovery from neuromuscular block after a 3x ED₉₀ dose of atracurium or vecuronium is similar in spiteof a three-fold difference in their elimination half-lives.We have investigated simultaneous spontaneous recovery fromequipotent doses of atracurium and vecuronium in the isolatedforearms of volunteers in order to attempt to explain this paradox.Simultaneous administration of the two drugs, one in each ofthe subject's forearms, allowed direct comparison of recoveryto be made against the same plasma concentration of drug. Therecovery index of atracurium was found to be significantly longerthan that of vecuronium. We suggest that this observation, whenconsidered with the different plasma concentrations after a3xED₉₀ dose, helps to explain the similar duration of actionof the two drugs during the recovery phase after a large systemicbolus. (Br. J. Anaesth. 1993; 71: 730–731)     

COMPARISON OF THE TRAIN-OF-FOUR FADE PROFILES PRODUCED BY VECURONIUM AND ATRACURIUM

In this double-blind study, we have allocated randomly 40 ASAI-III patients to one of four groups. After a standard anaestheticinduction, patients received vecuronium 0.08 mg kg^–1 or0.10 mg kg^–1, or atracurium 0.4 mg kg^–1 or 0.5 mgkg^–1. Using an electromyogram (Datex Relaxograph) thetrain-of-four (TOF) response was measured during onset of andrecovery from neuromuscular block. A greater degree of fadeof TOF was observed with atracurium during onset of neuromuscularblock than with equivalent doses of vecuronium. During recoveryof neuromuscular transmission, vecuronium was associated withmore fade than atracurium. The differences in the TOF profilesof these two drugs may be important when judging the adequacyof antagonism of neuromuscular block using the TOF response.     

NEUROMUSCULAR BLOCKING AND AUTONOMIC EFFECTS OF VECURONIUM AND ATRACURIUM IN THE ANAESTHETIZED CAT

The effects of vecuronium and atracurium on neuromuscular transmission,on the responses of the heart rate to vagal stimulation andon the responses to preganglionic stimulation of the nictitatingmembrane were compared in the chloralose-anaesthetized cat.Vecuronium was four times more potent than atracurium as a neuromuscularblocking agent, whereas the two compounds had similar potenciesin blocking the effects of stimulation of the cardiac vagus.The vagal/neuromuscular ratios measured at 50% inhibition were96 for vecuronium and 25 for atracurium. Vecuronium possesseda slightly shorter recovery time than atracurium and shorterduration of action on the soleus muscle. The onset times ofthe two compounds were not significantly different. Both compoundshad longer time-courses of action than suxamethonium. Very largedoses of vecuronium decreased the responses of the preganglionicstimulation of the nictitating membrane, suggesting that athigh doses the compound possesses ganglion blocking activity.Large doses of atracurium also decrease the nictitating membraneresponses and, in some cats, contractions of the nictitatingmembrane associated with increases in heart rate and arterialpressure were observed.     

SYNERGISTIC INTERACTION BETWEEN MIDAZOLAM AND PROPOFOL

We gave either midazolam or propofol for induction of anaesthesiato 140 ASA I or II female patients (18–60 yr). ED₅₀, valueswere obtained by probit analysis for three clinical end-points:loss of response to command; loss of eyelash reflex; failureto respond to application of an anaesthetic face mask delivering1 % isoflurane. Propofol ED₅₀ values (95% confidence intervals)were 1.25 (0.99–1.48) mgkg^–1, 1.61 (1.29–1.94)mg kg^–1 and1.51 (1.20–1.82) mg kg^–1, respectively.ED₅₀ values for midazolam were 0.26 (0.20–0.37) mg kg^–1,0.29 (0.23–0.47) mgkg^–1 and 0.25 (0.20–0.32)mg kg^–1, respectively. An additional 92 similar patientsreceived one of nine dose combinations of midazolam and propofolfor induction of anaesthesia, propofol being administered 2min after midazolam. Success of induction was based on the clinicalend-point of loss of response to command. Administration of25% of the ED₅₀ of midazolam followed by 50% of the ED₅₀ ofpropofol resulted in loss of response to command in 50 % ofpatients, while 50 % of the ED₅₀ of midazolam, followed by 25%of the ED₅₀ of propofol had the same effect. A probit regressionmodel specifying a synergistic interaction between midazolamand propofol fitted the data significantly better than a modelspecifying no interaction. ^*Present address, for correspondence: Department of Anaesthetics,Royal Group of Hospitals, Grosvcnor Road, Belfast BT12 6BA,N. Ireland