Resistance to rocuronium of rat diaphragm as compared with limb muscles

Background

Skeletal muscles are composed of different muscle fiber types. We investigated the different potency to rocuronium among diaphragm (DIA), extensor digitorum longus (EDL), and soleus (SOL) in vitro as well as to investigate the differences of acetylcholine receptors (AChRs) among these three typical kinds of muscles.

Materials and methods

The isolated left hemidiaphragm nerve-muscle preparations, the EDL sciatic nerve-muscle preparations, and the SOL sciatic nerve-muscle preparations were established to evaluate the potency to rocuronium. Concentration-response curves were constructed and the values of IC₅₀ were obtained. The density of AChRs at the end plate and the number of AChRs per unit fiber cross fiber area (CSA), AChR affinity for muscle relaxants were evaluated.

Results

The concentration-twitch tension curves of rocuronium were significantly different. The curves demonstrated a shift to the right of the DIA compared with the EDL and SOL (P < 0.01), whereas no significant difference was observed between EDL and SOL (P > 0.05). IC₅₀ was significantly largest in DIA, second largest in SOL, and smallest in EDL (P < 0.05). The number of AChRs per unit fiber CSA was largest in DIA, second largest in EDL, and smallest in SOL (P < 0.01 or P < 0.05). The DIA showed the lowest affinity of the AChRs, whereas the SOL showed the highest affinity.

Conclusions

The resistance to rocuronium of DIA compared with EDL and SOL was verified. The DIA was characterized by the largest number of AChRs per unit fiber CSA and the lowest affinity of the AChRs. Although compared with SOL, EDL was proved to have larger number of AChRs per unit fiber CSA and the lower affinity of the AChRs. These findings may be the mechanisms of different potency to rocuronium in DIA, EDL, and SOL. The results of the study could help to explain the relationship between different composition of muscle fibers and the potency to muscle relaxants. Extra caution should be taken in clinical practice when monitoring muscle relaxation in anesthetic management using different muscles.     

CONTINUOUS INFUSION OF MIVACURIUM IN CHILDREN

Mivacurium is a new short-acting competitive neuromuscular blockingagent. Infusion requirements for the maintenance of a stable90–99% muscle twitch depression were determined in 28children anaesthetized with nitrous oxide and 1% halothane (inspired)in oxygen or nitrous oxide in oxygen and opioid. Neuromuscularblock was assessed by monitoring the force of contraction ofthe adductor of the thumb during train-of-four (TOF) stimulationat 0.1 Hz. Infusion rate and twitch depression were analysedfrom 15 to 75 min and from 75 to 135 min after the start ofthe infusion. In the first period of evaluation, the mean infusionrequirement was 10.4 (SEM 0.92) µg kg^–1 min^–1during the halothane anaesthesia and 13 (1.4) µg kg^–1min^–1 during the opioid anaesthesia (P < 0.05). Thisdifference was present also during the second 60-min period.There was no significant correlation between infusion ratesrequired to maintain > 90% depression of the first twitch(T1) of the TOF and plasma cholinesterase concentrations. Regardlessof the anaesthetic regimen, children recovered rapidly afterdiscontinuing the infusion. The recovery index (25–75% recovery of T1) for all patients was 5.4 (0.57) min with nosignificant differences between the groups.     

DOSE-RESPONSE RELATIONSHIPS FOR EDROPHONIUM AND NEOSTIGMINE ANTAGONISM OF MIVACURIUM-INDUCED NEUROMUSCULAR BLOCK

We have studied the dose-response relationships for neostigmineand edrophonium during antagonism of neuromuscular block inducedby mivacurium chloride. Sixty-four ASA group I or II adultswere given mivacurium 0.15 mg kg^–1 during fentanyl-thiopentone-nitrousoxide-iso flurane anaesthesia. Train-of-four stimulation (TOF)was applied to the ulnar nerve every 10 s, and the force ofcontraction of the adductor pollicis muscle was recorded. Whenspontaneous recovery of first twitch height reached 10% of itsinitial control value, edrophonium 0.1, 0.2, 0.4, or 1 mg kg^–1or neostigmine 0.005, 0.01, 0.02, or 0.05 mg kg^–1 wasadministered by random allocation. Neuromuscular function inanother 16 subjects was allowed to recover spontaneously. Spontaneousrecovery from 90% mivacurium block to 95% twitch height andTOF ratio 0.75 occurred within 15 min. This study demonstratedthat the dose-response curves for these two drugs for antagonismof neuromuscular block (first twitch and train-of-four ratio)were parallel. The doses of neostigmine required to achieve50% (ED₅₀) and 70% (ED₇₀) recovery of the first twitch after10 min were 2 (1.5– 2.5) µg kg^–1 and 4.7 (4.1–5.4)µg kg^–1 (mean (95% confidence intervals)), respectively.Corresponding ED₅₀ and ED₇₀ values for edrophonium were 2.8(0.75–10.2) pg kg^–1 and 9.2 (3.6–23.6) µgkg^–1, respectively. These values corresponded to neostigmine:edrophonium potency ratios of 1.4 (0.4–2.4) and 1.95(0.9–2.9) for first twitch ED₅₀ and ED₇₀ height, respectively.The calculated doses producing 50% (ED₅₀ recovery of the TOFratio at 10 min were neostigmine 2.57 (1.8–3.6) µgkg^–1 and edrophonium 26.9 (14.6–49.6) pg kg^–1.These values corresponded to a potency ratio of 10.4 (0.7–20).(Br. J. Anaesth. 1993; 71: 709–714)     

CUMULATION OF NEOMYCIN AND ITS RESIDUAL POTENTIATION OF TUBOCURARINE IN THE CAT

Cumulation and interaction of neuromuscular blocking effectsof neomycin and tubocurarine were determined on responses ofthe tibialis anterior muscle of the anaezthetized cat to indirectstimulation. Neuromuscular block produced by neomycin was cumulativedespite rapid and apparent full recovery of twitch tension andan interval of 3 h between dose-response studies. ED₅₀ of neomycinon twitch tension decreased (P<0.05) from 22±4 mgkg^–1 to 12±3 mg kg^–1 after 3 h; marked post-tetanicexhaustion was observed after the antibiotic. Neuromuscularblock (80–90%) with neomycin 25–30 mg kg^–1followed by full recovery and a 3-h interval decreased (P<0.05)the ED₅₀ of tubocurarine on twitch tension from 0.2±0.02mg kg^–1 to 0.13±0.02 mg kg^–1. Tubocurarineexhibited no cumulative effects at intervals of 2 h and didnot significantly affect the response of twitch and tetanictension to neomycrn after an interval of 2 h. It is concludedthat neomycin increases the sensitivity of neuromuscular transmissionto tubocurarine despite apparently normal responses to indirectstimulation and that the post-tetanic exhaustion observed withneomycin alone may explain apnoea reported in patients withthe antibiotic.     

ONSET TIME AND DURATION OF ACTION FOR ATRACURIUM, ORG NC45 AND PANCURONIUM

Speed of onset, maximum block, duration of action and 10–25%recovery time for atracunum, OrgNC45 and pancuronium were determinedusing equipotent doses: 330 µg kg ^–1, 66µgkg ^–1 and 75µg kg ^–1 respectively Vein–to–muscleand artery-to-muscle onset times were measured by use of simultaneousrecordings. Mean speeds of onset to 95% twitch depression wereatracurium 2.7mm, Org NC45 2.8min and pancuronium 3 6 mm. Themedian value of maximum neuromuscular block exceeded 98 5% forall drugs and the mean durations of action to 25% recovery ofcontrol twitch height were: atracunum 27.6 min, Org NC 45 21.9min and pancuronium 45.1 min. The differences were statisticallysignificant The recovery period from 10% to 25% twitch responsewas considerably longer for pancuronium than for the other drugs,which did not differ significantly from each other. We wereunable to validate the artery–to–muscle techniquein the determination of onset time.     

INFUSION OF ATRACURIUM IN NEONATES, INFANTS AND CHILDREN: A Study of Dose Requirements

The doses of atracurium (by infusion) required to maintain steady-state(90–95%) neuromuscular block were assessed in 75 childrenaged 9 days to 17 yr during balanced anaesthesia. Followingthe intubating dose of atracurium 0.4 mg kg^–1 and afterthe recovery of single twitch to 5–10% of control (monitoredby evoked EMG of hypothenar muscle), an infusion of atracurium0.5 mg kg^–1 h^–1 was started. In 22 of the patientsthis initial rate resulted in the desired steady state; 32 patientsrequired one, and 21 required two or more adjustments in rate.The mean single twitch value at steady-state was 6.6±0.3%(SEM), which is equal to 93% neuromuscular block. The infusionrequirement to maintain the steady state neuromuscular blockin all paediatric patients more than 1 month old was constant(0.53±0.01 mg kg^–1 h^–1). The infusion requirementof neonates up to 1 month old was 25% less (0.40±0.02mg kg^–1 h^–1; P = 0.003). A significant correlation(n = 75, r = 0.76, P < 0.001) was found between the infusionrate (mg m^–2 h^–1) and the logarithm of the bodysurface area.     

COMPARISON OF NEUROMUSCULAR BLOCK IN THE DIAPHRAGM AND HAND AFTER ADMINISTRATION OF TUBOCURARINE, PANCURONIUM AND ALCURONIUM

The onset and offset of neuromuscular block in the diaphragmand in the adductor pollicis muscle were recorded using unilateralsupramaximal stimulation of phrenic and ulnar nerves. Thirtypatients were allocated randomly to receive tubocurarine 0.4–0.5mg kg^–1, pancuronium 0.07–0.08 mg kg^–1 oralcuronium 0.2–0.3 mg kg^–1. In all cases the onsetof neuromuscular block occurred in the diaphragm before adductorpollicis, and spontaneous recovery was evident first in thediaphragm. There was a correlation between the time of spontaneousreappearance of twitch in the diaphragm and in the adductorpollicis only in the patients who received pancuronium (r =0.97, P < 0.05 for reappearance of the first twitch of thetrain-of-four of each muscle). The duration of paralysis inthe diaphragm was less than 5 min in five patients who receivedtubocurarine and in one who received alcuronium; this correspondedto a period of paralysis in the adductor pollicis muscle ofmore than 25 min in each case.     

RECOVERIES OF POST-TETANIC TWITCH AND TRAIN-OF-FOUR RESPONSES AFTER ADMINISTRATION OF VECURONIUM WITH DIFFERENT INHALATION ANAESTHETICS AND NEUROLEPTANAESTHESIA

We have studied recovery of post-tetanic twitch (PTT) and train-of-four(TOF) responses after administration of vecuronium in 100 patientsunder different inhalation anaesthetics and neuroleptan-aesthesia.Patients were allocated randomly to five groups of 20 patientseach to receive: neuroleptanaesthesia (droperidol and fentanyl).halothane, isoflurane, enflurane or sevoflurane (1 MAC in nitrousoxide and oxygen). The times from initial administration ofvecuronium 0.2 mg kg^–1 to the first appearances of T1,T2, T3 and T4 differed significantly between groups. However,the intervals to the first appearance of PTT₁, PTT₁₀ and PTT₂₀did not differ significantly between groups. (Br. J. Anaesth.1993; 70: 402–404)     

MAINTENANCE OF CONSTANT 95% NEUROMUSCULAR BLOCKADE BY ADJUSTABLE INFUSION RATES OF PANCURONIUM AND ATRACURIUM

In a double-blind study, 39 patients (ASA groups I-II) weregiven either pancuronium or atracurium as an infusion duringsurgery. The drugs were given as an initial loading dose of0.064 mg kg^–1 or 0.30 mg kg^–1, respectively, followedby an infusion, the rate of which was regulated to produce aconstant 95% depression of the evoked twitch response throughoutsurgery. No significant difference in the number of correctionsof the infusion rate per hour was found (4.6 v. 4.9). Mean infusionmaintenance doses were 35 and 356 µg kg^–1 h^–1respectively. The inter-individual variability of maintenancedoses for the two drugs did not differ, the coefficients ofvariation being 0.32 and 0.24. On stopping the infusion, thepatients given atracurium recovered to a 15% twitch faster thanthose given pancuronium. In addition neostig-mine produced aquicker recovery in this group. Thus atracurium may be a moresatisfactory drug for use by infusion.     

ONSET AND RECOVERY OF ATRACURIUM AND SUXSMETHONIUM-INDUCED NEUROMUSCULAR BLOCKADE WITH SIMULTANEOUS TRAIN-OF-FOUR AND SINGLE TWITCH STIMULATION

Single twitch and train-of-four stuimulation were applied at0.08 Hz to each ulnar nerve and the force of contraction ofthe adductor pollicis was recorded during onset of and recoveryfrom neuromuscular blockade by suxamethonium 1mg kg^–1or atracuirm 0.4 mg kg^–1. Times to 90% first twitch blockadeof train-of-four were (mean ± SEM) 0.82 ± 0.08and 1.98 ± 0.18 min for suxmaethonium and atracurium,respectively, compared with times to 90% single twitch blockadeof 1.00±0.07 and 3.35 ± 0.37 min, respectively(p < 0.05 in both cases). Apparent onset time also dependedon how long train-of-four stimulation had been applied beforeinjection of atracurium. The mode of stimulation had littleeffect on time to 10% recovery. The results are consitent withstimulation-induced augmentation in muscle blood flow, whichincreased delivery of the drug to the neuromuscular junction.     

MYONEURAL EFFECTS OF PETHIDINE AND DROPERIDOL

In vitro experiments on the rat phrenic nerve - hemidiaphragmpreparation, stimulated directly or indirectly with supramaximalimpulses at 0.1 Hz revealed that pethidine in concentrationsgreater than 5µgml^–1 caused a rapid increase ofthe twitch. This was maximal (60% increase during direct and70% increase during indirect stimulation) with pethidine 75µgml^–1.With concentrations of pethidine greater than 40µgml^–1,the initial increase was followed by a slowly developing inhibitionof the twitch (50% depression with 46.0 and 50.4µgml^–1during direct and indirect stimulation, respectively). Droperidolcaused no increase in twitch, but it depressed the twitch by50% at concentrations of 9.8 and 6.9µgml^–1 duringdirect and indirect stimulation, respectively. The increasein twitch produced by pethidine was augmented by 4-aminopyridineand inhibited by verapamil during both direct and indirect stimulation.Tubocurarine antagonized the augmentation of the twitch by pethidineonly during indirect stimulation. The pethidine- and droperidol-inducedinhibition of the twitch could be reversed by washout, but itwas not antagonized by neostigmine or 4-aminopyridine. The inhibitoryeffect of pethidine and droperidol were additive. Sub-effectiveinhibitory concentrations of pethidine and droperidol, and thoseof tubocurarine, pancuronium and suxamethonium, independentlyof the sequence of their administration, mutually increasedthe myoneural effects of one another. The resulting twitch depressioncould be reversed by washout. The inhibition caused by the combinationof pethidine with tubocurarine or pancuronium was partiallyantagonized by neostigmine or 4-aminopyridine. That of pethidinewith suxamethonium was not affected by neostigmine or 4-aminopyridine.The findings indicate that the main site of both the facilitatingand inhibitory effect of pethidine, and that of the inhibitoryeffect of droperidol, it the muscle fibre. In addition, droperidolhas a moderate inhibitory and pethidine a weak stimulating effectat the neuromuscular junction.     

ONSET AND RECOVERY OF ROCURONIUM (ORG 9426) AND VECURONIUM UNDER ENFLURANE ANAESTHESIA

We have studied the onset, duration of action and recovery indexof twice the ED₉₀ of rocuronium (Org 9426) (0.6 mg kg^–1)and of vecuronium (0.08 mg kg^–1) in patients during enf/uraneanaesthesia. Rocuronium had a significantly shorter mean onsettime of 1.8 (SD 0.4) min, compared with vecuronium 3.4 (0.8)min. Clinical duration (time for the first twitch in the train-of-fourto recover to 25% of control) was similar for both drugs (29(10) min vs 31 (12) min). Spontaneous recovery times (TOF ratio70%) did not differ significantly between rocuronium (47 (10)min) and vecuronium (44 (11) min). (Br. J. Anaesth. 1992;69:511–512)     

PHARMACODYNAMICS OF ATRACURIUM DURING PROPOFOL, THIOPENTONE AND OPIOID ANAESTHESIA

We have assessed in 20 patients the accuracy and precision ofan infusion profile for atracurium, which continually set theinfusion rate to maintain stable muscle paralysis and a targetsteady state plasma concentration, when equilibrium betweenthe biophase and plasma had occurred. Muscle paralysis was stableafter 20 min, with a mean absolute drift in muscle paralysisin the succeeding 40 min of 0.13 (SD 0.07)% T1/Tc (height offirst twitch/height of control twitch) per min. The plasma samplesafter 30 min, which were assessed empirically as being in equilibriumwith the biophase, had an overall mean bias of 8.0 (SEM 3.7)% (P < 0.05) and an overall mean absolute prediction errorof 16.4 (SEM 2.5)% from the target steady state concentrationbeing delivered by the infusion. The profile was then used toestimate the steady state plasma concentration of atracuriumrequired to maintain 90% paralysis (C_p^ss₉₀), by manually adjustingthe delivered target concentration of the infusion until muscleparalysis was stable at 88–92% inhibition of T1/Tc for15–20 min, with three plasma samples taken over the next10 min. Measurements were completed within 60–90 min.The mean C^ss_p90 of atracurium with propofol was 1.039 (SD 0.224)ug ml^–1 (n = 10), with thiopentone 1.334 (0.378) µgml–1 (n = 10), and with opioidanaesthesia 0.915 (0.221)ug ml^–1 (n = 10). These differences in the C^ss_p90 explainsome of the variability in response which occurs with neuromuscularblocking drugs. The technique enables the Cpss90 of a myoneuralblocker to be determined by a simple model-independent method.     

COMPARISON OF ATRACURIUM-INDUCED NEUROMUSCULAR BLOCKADE IN NEONATES, INFANTS AND CHILDREN

The potency of atracurium was determined in neonates, infantsand children during thiopentone–fentanyl–nitrousoxide in oxygen anaesthesia using single dose–responsecurves. The effective doses producing 50% depression of thefirst twitch of the train-of-four were significantly lower inneonates and infants than in children (82 and 112 v. 135 µgkg^–1). Following a standard dose of atracurium 0.5 mgkg^–1, 95% depression of the first twitch occurred morerapidly in neonates than in children (0.9 v. 1.4 min), whilerecovery to 10% of the control twitch height occurred more rapidlyin neonates than in the other two groups (22.7 v. 29.7 and 28.6min). It is concluded that neonates and infants require lessatracurium to produce a given degree of neuromuscular blockadecompared with older children. However, prompt recovery can beexpected in all healthy paediatric patients following a standardintubating dose of atracurium 0.5 mg kg^–1.     

ISOBOLOGRAPHIC AND DOSE-RESPONSE ANALYSIS OF THE INTERACTION BETWEEN PIPECURONIUM AND VECURONIUM

We have studied the neuromuscular effects of pipecuronium, vecuroniumand their combination in 130 ASA group I or II patients. Patientswere anaesthetized with 0.8% halothane and 60% nitrous oxidein oxygen. Neuromuscular block was recorded as the evoked thenarmechanomyographic response to train-of-four stimulation of theulnar nerve (2Hz at 10-s intervals). The dose-response curveswere determined by probit analysis. The calculated doses producing50% depression of the first twitch height were 15.6, 16.9 and15.0 µg kg^–1 for the pipecuronium, vecuronium andpipecuronium-vecuronium combination groups, respectively. Isobolographic and algebraic (fractional) analyses were used to assessquantitatively the combined neuromuscular effect of pipecuroniumand vecuronium and to define the type of interaction betweenthese drugs. The interaction between pipecuronium and vecuroniumwas found to be additive. (Br. J. Anaesth. 1993; 71: 556–560)      

PROPOFOL POTENTIATES BOTH PRE- AND POSTSYNAPTIC EFFECTS OF VECURONIUM IN THE RAT HEMIDIAPHRAGM

We have measured twitch tension in response to train-of-fourstimulation in rat isolated phrenic nerve-hemidiaphragm preparations.Propofol inhibited nerve evoked twitch tension, with 50% inhibitionoccurring at 420 (sD 29) nwol litre^–1. Although propofol100 umol litre^–1 by itself had no effect on nerve evokedtwitch tension, it potentiated the neuromuscular blocking effectsof vecuronium. The decrease in train-of-four ratio with vecuroniumwas directly proportional to the degree of twitch inhibition,regardless of whether twitch was depressed by vecuronium aloneor in combination with propofol. The finding that the train-of-fourratio was a function of the degree of block, rather than simplya function of vecuronium concentration, indicates that propofolalso contributed to train-of-four fade and potentiated bothpre- and postsynaptic effects of the neuromuscular blocker.The concentrations of propofol used in this study are much greaterthan human therapeutic blood concentrations, which are typically25–35 jimol litre^–1 (4–6 ug ml^–1) immediatelyafter a bolus dose of 2 mg kg^–1, suggesting that neithermuscle weakness nor potentiation of vecuronium-induced neuromuscularblock should be of concern at propofol concentrations occurringclinically.     

PROLONGED PARALYSIS AFTER LONG-TERM, HIGH-DOSE INFUSION OF PANCURONIUM IN ANAESTHETIZED CATS

We have studied the neuromuscular effects of a 48-h infusionof high-dose pancuronium (400µg kg^–1 h^–1)in four cats anaesthetized with pentobarbitone, using contractionof tibialls anterior muscles after direct and indirect stimulation.After cessation of the pancuronium in fusion, prolonged paralysisexisted. The first twitch in the train-of-four stimuli (TOF)reappeared 8–12 h after termination of the pancuroniuminfusion. Twenty-four hours after termination of the infusion,TOF ratios were less than 0.08 and twitch contraction averaged39 (SE 8) % of initial values. Twitch contraction after directstimulation did not differ from initial values. Antagonism ofparalysis was accomplished with neostigmine 60 µg kg^–1in two animals and neostigmine 90 µg kg^–1 and 4-aminopyridine500 µg kg^–1 in the others. Steady-state plasma concentrationof pancuronium (2000 ng ml^–1) decreased rapidly aftertermination of the infusion, but then stabilized at about 130ng ml^–1. These results indicate that prolonged paralysisafter long-term administration of high-dose pancuronium is causedprimarily by failure of neuromuscular transmission, most likelycaused by the persistent plasma concentrations of the drug inthe pharmacologically active range. (Br. J. Anaesth. 1993; 71:393–397)     

Expression of Heat Shock Proteins (HSPs) in Aged Skeletal Muscles Depends on the Frequency and Duration of Exercise Training

The skeletal muscle in aged rats adapts rapidly following a period of exercise. This adaptation includes structural remodeling and biochemical changes such as an up-regulation of antioxidant enzymes, content of stress and heat shock proteins (HSPs). However, the associated molecular mechanisms mediating different types of exercise training-induced adaptations are not yet completely understood. Therefore, the purpose of this study was to investigate the effects of duration and frequency exercise on the expression of HSPs, antioxidant enzymes, and mitogen-activated protein kinase (MAPKs) in the skeletal muscles of aged rats. Young (3-month-old) and aged (20-month-old) male Sprague-Dawley rats were randomly assigned to 6 groups and extensor digitorum longus (EDL; fast twitch muscle fiber) and soleus (SOL; slow twitch muscle fiber) skeletal muscles were collected immediately. The expression pattern of HSPs in skeletal muscles was decreased in old groups compared with young groups. Especially, HSPs showed lower expression in SOL than EDL muscle. Interestingly, HSPs in aged rats was increased significantly after S1 (single long-duration; 1×30 min, 5 days/week for 6 weeks) and M1 types (multiple short-duration; 3×10 min·day⁻¹, 5 days·week⁻¹ for 6 weeks) than S2 (single long-duration; 1×30 min, 3 days/week for 6 weeks) and M2 (multiple short-duration; 3×10 min·day⁻¹, 3 days·week⁻¹ for 6 weeks) types of exercise training. Also, superoxide dismutase (SODs) showed similar expression as HSP did. On the contrary, the p-ERK and p-JNK were down regulated. In addition, p-p38 level in the SOL muscle was activated markedly in all exercise groups. These results demonstrate that increasing of HSP expression through duration and frequency exercise can lead to protection and training-induced adaptation against aging-induced structural weakness in skeletal muscles.

Key points

• The expression of heat shock proteins (HSPs) in aged rats was increased significantly after single long-duration (S1) and multiple short-duration (M1) types than S2 and M2 types of exercise training in soleus (SOL) skeletal muscles.
• Superoxide dismutase (SODs) showed similar expression as HSPs did. On the contrary, the p-ERK and p-JNK were down regulated. In addition, p-p38 level in the SOL muscle was activated markedly in all exercise groups.
• Induction of HSPs and SODs by high duration and frequency of exercise training such as S1 and M1 types with concomitant MAPKs pathway depending on the type of muscles.
• The frequency and duration of exercise training could affect the functional adaptation and protection against aging-induced structural weakness of skeletal muscles through changing expression of related molecules.

Key words: Aging, multiple short-duration exercise training, single long-duration exercise training, heat shock protein, superoxide dismutase, mitogen-activated protein kinase     

NEUROMUSCULAR BLOCKING EFFECTS OF VECURONIUM AND PANCURONIUM DURING HALOTHANE ANAESTHESIA

The neuromuscular blocking properties of vecuronium (Org NC45) and pancuronium were compared in 40 patients during halothaneanaesthesia. Onset time was found to be dose-dependent, butno significant difference was found between the two drugs. Theduration of action of vecuronium was significantly shorter thanpancuronium. Times to 90 recovery of twitch height followingvecuronium 0.03 mg kg^–1 and 0.057 mgkg^–1 were 32.0min and 44.9 min, respectively, compared with 72.9 min and 124.7min following equipotent doses of pancuronium (0.042 mg kg^–1and 0.08 mg kg^–1). Recovery indices following both dosesof vecuronium (10.0 min and 11.8 min) were significantly shorterthan after pancuronium (31.0 min and 46.9 min). The reversaltimes of vecuronium (times from 10 to 90 twitch height recovery)were significantly shorter than those of pancuronium (7.9 minand 7.3 min, respectively, compared with 17.1 min and 17.7 min).     

Studies on the possible role of thyroid hormone in altered muscle protein turnover during sepsis.

Five days after thyroidectomy (Tx) or sham-Tx in young male Sprague-Dawley rats, sepsis was induced by cecal ligation and puncture (CLP). Control animals underwent laparotomy and manipulation of the cecum without ligation or puncture. Sixteen hours after CLP or laparotomy, protein synthesis and degradation were measured in incubated extensor digitorum longus (EDL) and soleus (SOL) muscles by determining rate of 14C-phenylalanine incorporation into protein and tyrosine release into incubation medium, respectively. Triiodothyronine (T3) was measured in serum and muscle tissue. Protein synthesis was reduced by 39% and 22% in EDL and SOL, respectively, 16 hours after CLP in sham-Tx rats. The response to sepsis of protein synthesis was abolished in Tx rats. Protein breakdown was increased by 113% and 68% in EDL and SOL, respectively, 16 hours after CLP in sham-Tx animals. The increase in muscle proteolysis during sepsis was blunted in hypothyroid animals and was 42% and 49% in EDL and SOL, respectively. T3 in serum was reduced by sepsis, both in Tx and sham-Tx rats. T3 in muscle, however, was maintained or increased during sepsis. Abolished or blunted response of muscle protein turnover after CLP in hypothyroid animals may reflect a role of thyroid hormones in altered muscle protein metabolism during sepsis. Reduced serum levels of T3, but maintained or increased muscle concentrations of the hormone, suggests that increased T3 uptake by muscle may be one mechanism of low T3 syndrome in sepsis, further supporting the concept of a role for thyroid hormone in metabolic alterations in muscle during sepsis.