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Complete ischemia and reperfusion effects on twitch force (∫(F·t)), twitch latent period (TLP), maximal rate of rise of twitch tension (δF/δt)max, and twitch maximum relaxation rate (TMRR) were assessed. We divided 36 adult rats into four groups; two control groups (n = 9), a group undergoing 1 hour of ischemia followed by 1 hour of reperfusion (n = 9), and one group exposed to 2 hours of ischemia followed by 1 hour of reperfusion (n = 9). We have induced twitch contractions every 10 minutes in the soleus and the extensor carpi radialis longus (ECRL). Twitch contractions were recorded and then analyzed for ∫(F·t), TLP, (δF/δt)max, and TMRR. During 1 hour and 40 minutes of ischemia, TLP increased to 179 ± 24% (p < 0.05) in the soleus and to 184 ± 16% (p < 0.05) in the ECRL, an effect that was partially recovered during 1 hour of reperfusion. This increase started after 20 minutes of ischemia in the soleus and after 40 minutes of ischemia in the ECRL. The increase was faster in the ECRL and peaked at the same time for both muscular groups. ∫(F·t) and (δF/δt)max decreased during 1 hour of ischemia to 46 ± 7% (p < 0.05) in the soleus and to 40 ± 7% (p < 0.05) in the ECRL. TMRR decreased during 1 hour of ischemia to 39 ± 5% (p < 0.05) in the soleus and to 54 ± 8% (p < 0.05) in the ECRL. During 1 hour of reperfusion all of them recovered close to control values.

Background Gentamicin reduces acetylcholine release and clindamycin causes end-plate ion channel blockade. Because of these reasons, two drugs show muscular relaxant effect and potentiate the action of nondepolarizing neuromuscular agents. This study was intended to evaluate the effect of gentamicin and clindamycin on rocuronium-induced neuromuscular blockade and the interaction between these drugs. Methods Male Sprague-Dawley rats' phrenic nerves and diaphragms were installed in a bath containing Krebs solution. They were divided into three study groups. The first group was pre-treated with 0.1 (n = 3), 0.2 (n = 4) or 0.5 (n = 3) mM gentamicin and the tension was measured as the concentration of rocuronium was increased. The second group was experimented by increasing gentamicin on 0.25 (n = 5), 0.5 (n = 6) or 1.0 (n = 6) mM clindamycin. The final group was pre-treated with various combinations of gentamicin and clindamycin. The drug concentration was gradually increased until single twitch tension decreased by around 80%. Effective concentration was calculated using a probit model and interaction indices derived the Loewe additivity. Results The administration of gentamicin and the combination of gentamicin and clindamycin enhanced rocuronium-induced neuromuscular blockade. At 0.2 and 0.5 mM gentamicin, synergistic interactions with rocuronium were observed. Likewise, at 0.5 and 1.0 mM clindamycin, synergistic interactions with gentamicin appeared. When all three drugs were combined, in the tetanic fade, all the groups except for those administered with 0.01 mM gentamicin and 0.25 mM clindamycin showed synergistic interactions. Conclusions This study demonstrate that gentamicin and clindamycin potentiated rocuronium induced neuromuscular blockade. Moreover, it was found that these drugs interacted synergistically.

1. Spontaneously beating atria from frogs (R. pipiens) and eels (A. anguilla) were compressed hydraulically to 10 MPa. Effects on beating frequency and twitch tension were studied. 2. At low temperatures (8-10 degrees C) compression to 10 MPa caused a slowing of the beat frequency. No effects were noted at higher temperatures (16-24 degrees C). Twitch tension was decreased by pressure at low temperatures and increased at high temperatures. 3. Differences were noted between preparations from cold and warm acclimatized frogs, and from silver and yellow eels, respectively. 4. The effect of temperature acclimatization on pressure and temperature sensitivity is discussed in relation to data on cardiac phospholipid fatty acid composition.

The superimposed twitch technique was used to study the effect of whole-body hypothermia on maximal voluntary activation of elbow flexors. Seven subjects [26.4 ± 4 years old (mean ± SD)] were exposed to 60 min of either immersion in 8°C water (hypothermia) or sitting in 22°C air (control). Voluntary activation was assessed during brief (3 s) maximal voluntary contractions (MVCs) and then during a 2 min fatiguing sustained MVC. Hypothermia (core temperature 34.8 ± 0.9°C) decreased maximal voluntary torque from 98.2 ± 1.0 to 82.8 ± 5.8% MVC (P < 0.001) and increased central conduction time from 7.9 ± 0.4 to 9.1 ± 0.7 ms (P < 0.05). Hypothermia also decreased maximal resting twitch amplitude from 17.6 ± 4.0 to 10.0 ± 1.7% MVC (P < 0.005) and increased the time-to-peak twitch tension from 55.4 ± 4.0 to 79.0 ± 11.7 ms (P < 0.001). During the 2 min contraction, hypothermia decreased initial torque (P < 0.01) but attenuated the subsequent rate of torque decline (control from 95.5 ± 4 to 29.4 ± 8% MVC; and hypothermia from 85.3 ± 8 to 37.3 ± 5% MVC; P < 0.01). Cortical superimposed twitches increased as fatigue developed but were always lower in the hypothermic conditions. Cortical superimposed twitches increased from a value of 0.4 ± 0.3% MVC prefatigue to 3.9 ± 1.4% MVC postfatigue (P < 0.001) in the hypothermic conditions and from 1.7 ± 0.9 to 5.5 ± 2.3% MVC in control conditions. Our results suggest that hypothermia decreases MVCs primarily via peripheral mechanisms and attenuates the rate of fatigue development by reducing central fatigue.

Anecdotal observations suggest that low frequency fatigue, as judged by a fall in twitch tension, is more difficult to achieve in the diaphragm than nonrespiratory muscle but this hypothesis has not previously been directly tested. We studied 7 subjects by performing incremental repetitive contraction loading protocols of the diaphragm and quadriceps. We measured twitch transdiaphragmatic pressure (Tw Pdi) and twitch quadriceps tension (Tw Q) during both muscle contraction and relaxation phases during the run. Unpotentiated and potentiated Tw Pdi and Tw Q were measured before and at 20, 40, and 60 minutes after the run. During the run, greater activation of the quadriceps was achieved; for example, at 70% of maximal voluntary effort the interpolated Tw Q was 12.5% of the relaxation phase Tw Q (implying activation of 87.5%) compared with 29.4% (i.e., 70.6% activation) for the diaphragm (p = 0.05). A significantly greater fall in Tw Q than Tw Pdi was observed (unpotentiated Tw Pdi at 20 minutes 94% baseline versus Tw Q 59% baseline, p = 0.007). Low frequency fatigue in humans is more difficult to generate in the diaphragm than in the quadriceps muscle due in part to reduced central activation.

The effects of a ramp stretch (amplitude < 6% muscle fibre length (L0), speed < 13L0 s−1) on twitch tension and twitch tension re-development were examined in intact mammalian (rat) fast and slow muscle fibre bundles. The experiments were done in vitro at 20°C and at an initial sarcomere length of 2.68 μm. In both fibre types, a stretch applied during the rising phase of the twitch response (including the time of stimulation) increased the re-developed twitch tension (15–35%). A stretch applied before the stimulus had little or no effect on the twitch myogram in fast muscle fibres, but it increased the twitch tension (∼5%) in slow muscle fibres. A similar stretch had little or no effect on tetanic tension in either muscle fibre type. In general, the results indicate that the contractile-activation mechanism may be stretch sensitive and this is particularly pronounced in slow muscle fibres. Recorded at a high sampling rate and examined at an appropriate time scale, the transitory tension response to a stretch rose in at least two phases; an initial rapid tension rise to a break (break point tension, P1a) followed by a slower tension rise (apparent P2a) to a peak reached at the end of the stretch. Plotted against stretch velocity, P1a tension increased in direct proportion to stretch velocity (viscous-like) whereas, P2a tension (calculated as peak tension minus P1a tension) increased with stretch velocity to a plateau (visco-elastic). Examined at the peak of a twitch, P1a tension had a slope (viscosity coefficient) of 1.8 kNm−2 per L0 s−1 in fast fibres and 4.7 kNm−2 per L0 s−1 in slow muscle fibres. In the same preparations, P2a tension had a relaxation time of 8 ms in the fast muscle fibres and 25 ms in the slow muscle fibres. The amplitudes of both tension components scaled with the instantaneous twitch tension in qualitatively the same way as the instantaneous fibre stiffness. These fast/slow fibre type differences probably reflect differences in their cross-bridge kinetics.

1. The purpose of this study was to assess the potential of various preservation solutions, originally designed for solid organs, to protect muscle function during cold storage. 2. The soleus (SOL) and the cutaneous trunci (CT) muscle from the rat were isolated and stored for 2, 4 or 8 h at 10°C. The solutions used, listed in order from an intracellular to an extracellular-like composition, were: University of Wisconsin (UW), Euro-Collins (EC), HTK-Bretschneider (HTK), reversed St. Thomas' Hospital (ST2) and Krebs-Henseleit (KH). After cold storage, the muscles were tested by direct electrical stimulation to obtain the maximum twitch tension (Pt) and the maximum tetanus tension (P0). Subsequently, the muscles were prepared for morphological analysis. 3. In general, storage at 10°C caused a gradual decrease of Pt and P0 with time. After 8 h of storage in the extracellular-like solutions KH and ST2, the P0 was about 50% (SOL) and 35% (CT) of control. Eight hours of storage in intracellular-like solutions resulted in a P0 of 50% of control for HTK, in a P0 of 40% (SOL) and 67% (CT) for UW, but in a P0 of 5% (SOL) and 26% (CT) for EC. These findings corresponded well with the morphological observations. 4. It is concluded that the effects of 10°C storage on skeletal muscle function are not predominantly determined by the intra- or extracellular-like composition of the solutions used. Both UW and HTK were most effective (P0 > 50% of control) in preserving muscle function.

An elevated heat-shock protein (HSP) content protects cells and tissues, including skeletal muscles, from certain stressors. We determined if heat stress and the elevated HSP content that results is correlated with protection of contractile characteristics of isolated fast and slow skeletal muscles when contracting at elevated temperatures. To elevate muscle HSP content, one hindlimb of Sprague–Dawley rats (21–28 days old, 70–90 g) was subjected to a 15 min 42 °C heat-stress. Twenty-four hours later, both extensor digitorum longus (EDL) and soleus muscles were removed, mounted in either 20 °C or 42 °C Krebs-Ringer solution, and electrically stimulated. Controls consisted of the same muscles from the contra-lateral (non-stressed) hindlimbs as well as muscles from other (unstressed) animals. Isolated muscles were twitched and brought to tetanus every 5 min for 30 min. As expected, HSP content was elevated in muscles from the heat-stressed limbs when compared with controls. Regardless of prior treatment, both EDL and soleus twitch tensions were lower at 42 °C when compared with 20 °C. In addition, when incubated at 42 °C, both muscles showed a drop in twitch tension between 5 and 30 min. For tetanic tension, both muscles also showed an increase in tension between 5 and 30 min when stimulated at 20 °C regardless of treatment but when stimulated at 42 °C no change was observed. No protective effect of an elevated HSP content was observed for either muscle. In conclusion, although heat stress caused an elevation in HSP content, no protective effects were conferred to isolated contracting muscles.

In single frog skeletal muscle fibers, picrotoxin (5 mM) potentiated the voltage-dependent component of contractions in response to 2-s depolarizing pulses while greatly inhibiting the simultaneously recorded tubular Ca current in a normal-Ca, Na- and CI-deficient solution, provided the contractions were generated at long time intervals (2 min). In normal Ringer's solution, picrotoxin reversibly increased the amplitude of the early large birefringence signal and the amplitude and duration of the simultaneously recorded twitch tension, suggesting that the drug may increase, directly or indirectly, the release of Ca from the SR.

Objective: To study the influence of hypothermic cardiopulmonary bypass (CPB) on the pharmacodynamics and pharmacokinetics of rocuronium. Design: Prospective, descriptive study. Setting: Operating room at a university hospital. Participants: Ten ASA class III end IV patients, ranging in age from 35 to 75 years, scheduled for elective coronary artery bypass grafting. Interventions: Neuromuscular transmission was monitored mechanomyographically. The time course of action of maintenance doses and plasma concentration-response relationships were determined before, during, and after OPE. The plasma concentration decay and renal elimination were studied simultaneously. Plasma and urine concentration of rocuronium ware determined by high-performance liquid chromatography. Measurements and Main Results: Hypothermic CPB prolonged the duration of action of coincided with a lower plasma concentration at a twitch response of 5% of control. The duration of action of maintenance doses returned to prehypothermic CPB level after rewarming to a nasopharyngeal temperature of 37 degrees C. The plasma concentration-response relationship did not return to precooling control value, probably owing to persisting peripheral hypothermia. Both the renal elimination of rocuronium and the plasma concentration decay after the last maintenance dose under normothermic conditions resembled values obtained in patients not undergoing hypothermic CPB. Conclusions: Hypothermic CPB prolongs the duration of action of maintenance doses and alters the plasma concentration-response relationship of rocuronium. These changes may be the result of, on the one hand, an increased sensitivity of the neuromuscular transmission and/or decreased muscle contractility and, on the other hand, the result of a reduced plasma clearance during hypothermia. (C) 1995 by W.B. Saunders Company

Background An investigation suggested that neostigmine may not effectively antagonize mivacurium, presumably because neostigmine impairs mivacurium's metabolism. However, the effect of neostigmine on mivacurium's metabolism in vivo has not been reported. Therefore, the effect of neostigmine on neuromuscular function and plasma mivacurium concentrations during constant mivacurium infusion was determined. Methods Mivacurium was infused in five patients to maintain 90% depression of adductor pollicis twitch tension, then 50 micrograms/kg intravenous neostigmine was administered without altering the mivacurium infusion. Peak twitch tension after neostigmine, plasma cholinesterase activity, and mivacurium concentrations before and after neostigmine were measured. Five additional patients were given 50 micrograms/kg neostigmine to antagonize block due to continuous infusions of vecuronium. Results Neostigmine produced less antagonism of mivacurium (39 +/- 11%) than of vecuronium (54 +/- 9%, P < 0.05). Neostigmine decreased plasma cholinesterase activity and increased plasma concentrations of the trans-trans and cis-trans stereoisomers of mivacurium (P < 0.05). Conclusions Neostigmine is less effective at antagonizing the neuromuscular effect of mivacurium than that of vecuronium during constant infusion. Neostigmine increases plasma mivacurium concentrations, likely explaining its limited efficacy. Our results confirm that neostigmine impairs the metabolism of mivacurium in vivo and may explain the observation that neostigmine may not effectively antagonize mivacurium-induced block.

International audience; BACKGROUND AND PURPOSE The µ-conopeptide family is defined by its ability to block voltage-gated sodium channels (VGSCs), a property that can be used for the development of myorelaxants and analgesics. We performed a pharmacological characterisation of a new µ-conopeptide (μ-CnIIIC) on multiple preparations and molecular targets to gauge its potential as a myorelaxant. EXPERIMENTAL APPROACH The µ-CnIIIC was sequenced, synthesized, and characterized by its ability to block directly-elicited twitch tension in mouse skeletal muscle and action potentials in mouse sciatic and pike olfactory nerves. µ-CnIIIC was also studied on HEK-293 cells expressing various rodent VGSCs. Pharmacological investigations were extended to voltage-gated potassium channels and nAChRs to assess cross-interactions. Nuclear magnetic resonance (NMR) experiments were carried out for structural data. KEY RESULTS Synthetic μ-CnIIIC potently decreased twitch tension in mouse hemidiaphragms (IC(50) = 150 nM), and displayed a higher blocking effect in mouse extensor digitorum longus muscles (IC = 46 nM), as compared to µ-SIIIA, µ-SmIIIA and µ-PIIIA. μ-CnIIIC blocked Na(V) 1.4 (IC(50) = 1.3 nM) and Na(V) 1.2 in a long-lasting manner. Cardiac Na(V) 1.5 and DRG-specific Na(V) 1.8 were not blocked at 1 μM. An activity was unveiled on the α3β2 nAChR subtype (IC(50) = 450 nM) and, to a lesser extent, on the α7 and α4β2 subtypes. Structure determination of µ-CnIIIC revealed some similarities to α-conotoxins acting on nAChRs. CONCLUSION AND IMPLICATIONS μ-CnIIIC potently blocks VGSCs in skeletal muscle and nerve, and hence is applicable to myorelaxation. Its new atypical pharmacological profile suggests some common structural features between VGSCs and nAChR channels.

1. Force responses to ramp stretches were recorded in single muscle fibres isolated from the lumbricalis muscle of the frog. Stretches were applied at rest and at progressively increasing times after a single stimulus. 2. The increase of fibre stiffness that precedes tension development has a 'static' component that accounts for the whole fibre stiffness increase during the latent period and at very low tension at the beginning of the twitch. 3. Static stiffness increase was not affected by 2,3-butanedione-2-monoxime, a drug that almost completely inhibited twitch tension. 4. Static stiffness increased approximately 5-fold as the sarcomere length was increased from 2.1 to 2.84 microns. 5. These results suggest that static fibre stiffness increase is not attributable to the formation of non-force-generating cross-bridges.

The effects of propylene glycol (PG) on frog nerve-muscle preparations were examined to determine whether it has an effect on neuromuscular transmission and, if so, to elucidate the mode of the action. PG (5%, v/v) increased the twitch tension to over twice the control value. PG at concentrations above 0.2% significantly increased the amplitude of the endplate potential. PG (1%) raised the frequency of the miniature endplate potentials and increased their amplitude. These results show that PG both facilitates transmitter release from the nerve terminals and raises the acetylcholine sensitivity of the muscle endplate.

We measured the contractile properties of the first dorsal interosseous muscle by surface electrodes and needle electrodes during submaximal voluntary contraction. Twenty-seven single motor units were recorded from 5 volunteers by surface electrodes, which were confirmed by subsequent needle electrode recordings. Twitch tension ranged from 0.6 to 10.0 g with a mean of 3.7 g based on an averaging method triggered by surface myoelectric signals, and the tension calculated from the needle myoelectric signals ranged from 0.8 to 11.7 g with a mean of 3.6 g. Rise time ranged from 33.9 to 81.6 msec with a mean of 49.4 msec for the surface electrode recordings, and from 33.0 to 73.2 msec with a mean of 50.8 msec for the needle electrode recordings. The obtained data of surface electrode recordings indicated a high correlation with that of the needle electrode recordings, r = 0.92 (P < 0.001) for twitch tension and r = 0.91 (P < 0.001) for rise time. We also found a positive correlation between threshold force and twitch tension (by surface electrodes: r = 0.71, P < 0.05; by needle electrodes: r = 0.77, P < 0.05). Our studies indicate that it is possible to record single motor units by non-invasive surface electrodes provided that the unit has a threshold force of less than 2 kg.

Sevoflurane was compared to isoflurane anesthesia alone and in combination with atracurium or vecuronium in 84 rats using the sciatic nerve-anterior tibialis muscle preparation. Both bolus injection and infusion rate techniques were used to evaluate these drug interactions. The ED(50) (dose which produced a 50% depression of twitch tension) of atracurium was 311 +/- 31 and 360 +/- 32 microg.kg(-1) during 1.25 MAC sevoflurane and isoflurane anesthesia respectively. The ED(50) of vecuronium was 190 +/- 27 and 149 +/- 14 microg.kg(-1) during 1.25 MAC sevoflurane and isoflurane anesthesia respectively. The mean infusion rates of atracurium and vecuronium required to maintain a 50% depression of twitch tension were 5.04 +/- 0.7 and 2.02 +/- 0.3 mg.kg(-1).hr(-1). These infusion rates were 5.04 +/- 0.7 and 2.02 +/- 0.3 mg.kg(-1).hr(-1) during 1.25 MAC sevoflurane and 3.73 +/- 0.3 and 1.81 +/- 0.4 mg.kg(-1).hr(-1) during 1.25 MAC isoflurane anesthesia respectively. With both atracurium and vecuronium, the infusion rate required to maintain a 50% depression twitch of tension was inversely related to the concentrations of isoflurane and sevoflurane. The authors conclude that sevoflurane is similar in potency to that of isoflurane in augmenting a vecuronium or atracurium induced neuromuscular blockade in a dose-dependent manner.

PubMedID: 19855921 The purpose of this study was to investigate the effects of telmisartan (5 × 10-5 M) on the mechanical response of left ventricular papillary muscle in rats with streptozotocin-induced diabetes mellitus. We studied 32 rats; 16 were rendered diabetic by a single intravenous injection of streptozotocin (45 mg kg-1 i.v.) and 16 formed a non-diabetic control group. Diabetic animals were divided into two groups: diabetic-telmisartan group and the diabetic-control group. Non-diabetic controls were further divided into the non-diabetic-telmisartan group and the non-diabetic-control group. We found: (1) Muscle twitch tension (P 0) and contraction and relaxation rates were significantly lower in diabetic controls than in the other groups. (2) Telmisartan significantly increased P 0 in both diabetic and non-diabetic rats. (3) Times to peak tension and half-relaxation were significantly greater in groups DC and DT than in the non-diabetics. In conclusion, our data suggest that telmisartan attenuates diabetes-induced impairment of diabetic rat papillary muscles, and may thus be able to reduce cardiac complications in diabetes. © 2009 Springer-Verlag.

The running speed of Agama stellio stellio was 2.1 ± 0.3 m s−1 at preferred body temperature (Tb, 30°C). To account for sprint locomotion, we meaured two mechanical parameters and examined the ultrastructural features of a major locomotory muscle in normal walking and running locomotion, the iliofibularis muscle, which is considered to act as an extensor of the lower hind limb. The time to peak isometric twitch tension and time to half relaxation were 52 ± 7 ms and 76 ± 5 ms, respectively. The comparative ultrastructure of the fast and slow fibes provides structure-to-function correlation. The sarcoplasmic reticulum and T-tubules system are abundant in fast fibres which serve to transmit Ca2+ and spread the excitatory impulse intracellularly with great rapidity. In contrast, the membranous system of slow fibres is relatively poor and this indicates slow impulse propagation. Thus, these results show that the fast locomotion of Agama stellio stellio can, in part, be explained by the physiology and ultrastructure of the fibres of the locomotory muscles.

Generalizations of the integrated model describing the interaction of nondepolarizing neuromuscular blocking drugs with reversible anticholinesterase drugs described in Unadkat et al. (1) are reported. The models can deal with possible incomplete reversal (irreversible block) and/or noninstantaneous anticholinesterase kinetics. Experimental data were obtained from 22 human volunteers. Different levels of steady-state vecuronium block were induced in each volunteer (in the range of 50% to 95%), and reversed by short infusions of edrophonium (10 volunteers) or neostigmine (12 volunteers). Edrophonium or neostigmine concentrations and twitch tension (measured as the force of thumb adduction) were measured. The generalized integrated models fit the data well. In the case of neostigmine we find a nondistributional delay in its action. We relate this delay to the slow decarbamylation rate of the (neostigmine-induced) carbamylated anticholinesterase observed in vitro, and are able to model such noninstantaneous anticholinesterase kinetic processes. For both edrophonium and neostigmine we detect an inverse relationship between the (induced) level of initial block and maximal percentage recovery.

Intramuscular electrodes were used to study discharge variability in motor units of human masseter whose physiological properties were determined using spike-triggered averaging. Subjects voluntarily controlled the mean firing rate of a selected motor unit at 10 Hz for 15 min of continuous activation. Discharge variability was assessed at the beginning and end of this period. In 81% of units, the discharge variability at a mean interspike interval (ISI) of 100 ms increased after 15 min of continuous activity. There was a wide range of discharge variability within the population of masseter units studied, but no significant correlations were found between initial discharge variability and recruitment threshold, twitch tension or time-to-peak tension (TTP). There was, however, a significant correlation between motor unit fatigability and its initial discharge variability. This represents a link between the motoneuron and the functional properties of the muscle fibers in innervates.

Changes in blood properties and the chemical components, histology and isometric twitch tension of lateral muscle were studied in carp, Cyprinus carpio L., showing clinical signs of sekoke disease induced by a diet containing oxidized oil. When compared to normal fish, sekoke fish were found to have significantly lower mean blood pH, haematocrit, haemoglobin concentration and muscle water content. However, plasma lactate, lipoperoxide and total lipid concentrations were significantly higher in sekoke fish. It was found that in sekoke fish the maximum tension and the number of isometric twitches leading to complete fatigue of lateral muscle were greatly reduced. Histological studies confirmed that these reductions were related to the degree of structural damage within this tissue.

We evaluated the neuromuscular reversal with edrophonium using peripheral nerve stimulator and recorder in a patient with malathion intoxication. Edrophonium 10 mg i.v. caused an increase in single twitch tension by 76% of the control during the recovery phase from an acute cholinergic crisis 16 days after ingestion of malathion solution. The present study indicated that edrophonium test seems to be a reliable monitoring in evaluating neuromuscular reversal in the patient with acute malathion insecticide poisoning.

Magnetic stimulation of the femoral nerve has been shown to evoke maximal quadriceps twitch contraction (TwQ(max)). Its measurement as a nonvolitional index of muscle strength has been proposed as a means to follow the disability of patients with neuromuscular disorders or peripheral muscle weakness. The aim of the present study was to investigate TwQ(max) sensitivity to interventions known to develop peripheral muscle strength. We thus measured changes in TwQ(max) after a short-duration resistance training program, examining its reproducibility and comparing its changes with other indices of muscle strength, such as maximal voluntary contraction (MVC) and one-repetition maximum (1-RM). In 23 subjects, TwQ(max)was measured on two occasions. High within- and between-session intraclass coefficients of correlation were observed (r > 0.99). Within-session and between-session differences in TwQ(max)were low (2.2 +/- 1% and 5.4 +/- 2%, respectively). Eight subjects subsequently participated in a resistance training program of the knee extensors, 3 days per week for 8 weeks. TwQ(max) and 1-RM increased significantly after training (10.9 +/- 3.7 vs. 12.3 +/- 4.4 kg, P < 0.04; and 45 +/- 13 vs. 55 +/- 12 kg, P < 0.001, respectively), whereas the MVC increase did not reach significance (41.9 +/- 16 kg vs. 42.3 +/- 15 kg, P = 0.25). Responses to magnetic stimulation of the femoral nerve are highly reproducible and sensitive enough to detect improvement in muscle contractile mechanisms after resistance training in healthy subjects. Patient cooperation is not required, which may be an advantage in clinical situations.

Magnetic stimulation of the femoral nerve is a new technique for assessment of quadriceps strength by measurement of twitch tension (TwQ), a test that is independent of subject motivation. In this study, we sought to establish better define normal values by measurement of TwQ in 45 normal subjects. Supramaximal stimulation, as judged by TwQ, was achieved in 43 of 45 subjects at a mean of 90% of maximum stimulator output. The mean TwQ was 7.3 kilograms force (kgf) (SD 2.3) for women and 9.8 kgf (SD 2.5) for men. The mean maximal voluntary contraction (MVC) force was 48.0 kgf (SD 9.2) for women and 70.1 kgf (15.2) for men. The mean TwQ/MVC ratio was 0.15 for both women and men. Significant correlations were observed between TwQ and weight (r = 0.33, P

Diabetes mellitus affects skeletal muscle and free radicals may be implicated in the manifestation of diabetes complications. The present study investigated effects of alpha-tocopherol on diabetic dorsiflexor muscle via recording resting membrane potentials (RMPs), endplate potentials (EPPs), miniature endplate potentials (MEPPs) and isometric twitch tensions. Forty mice were divided randomly into two groups (n = 20). One group served as control and the other was injected once with streptozotocin (STZ) solution (60 mg/kg, i.p) to induce diabetes. The animals were then divided further into two subgroups (n = 10). Alpha-tocopherol (100 mg/kg, i.p) was administered daily to one control and one diabetic group for 3 weeks prior to recording day. Experiments were conducted 4 weeks following diabetes induction. Isometric twitch tension was measured in anaesthetized mice (2 mg/g urethane, i.p) via a transducer connected to a computer system. Resting membrane potentials and MEPPs were measured by utilizing the intracellular recording method. Compared to control, diabetic mice showed reduced twitch tension (4.4 +/- 0.4 g control vs. 2.5 +/- 0.3 g diabetic) and demonstrated delayed half time of decay. Diabetic flexor muscle also displayed significant reduction in MEPPs frequencies with no changes in RMPs. Alpha-tocopherol reversed tension reduction in diabetic mice (from 2.5 +/- 0.3 to 3.8 +/- 0.4 g), impacted delayed half time of decay and reversed reduction in MEPPs frequencies. Alpha-tocopherol exerts a protective role against diabetes-induced peripheral muscle dysfunction. This effect is probably mediated via a free radical scavenging mechanism or modification of Ca2+ homeostasis.

Structural changes in frog skeletal muscle were studied using x-ray diffraction with a time resolution of 0.53-1.02 ms after a single electrical stimulus at 8 degrees C. Tension began to drop at 6 ms (latency relaxation), reached a minimum at 8 ms, and then twitch tension developed. The intensity of the meridional reflection at 1/38.5 nm(-1), from troponin molecules on the thin filament, began to increase at 4-5 ms and reached a maximum at approximately 12 ms. The meridional reflections based on the myosin 43-nm repeat began to decrease when the tension began to develop. The peak position of the third-order myosin meridional reflection began to shift toward the higher angle at approximately 5 ms, reached a maximum shift (0.02%) at 10 ms, and then moved toward the lower angle. The intensity of the second actin layer line at 1/18 nm(-1) in the axial direction, which was measured at 12 degrees C, began to rise at 5 ms, whereas the latency relaxation started at 3.5 ms. These results suggest that 1), the Ca(2+)-induced structural changes in the thin filament and a structural change in the thick filament have already taken place during latency relaxation; and 2), the Ca(2+) regulation of the thin filament is highly cooperative.

A computer-controlled system has been developed to generate isometric recruitment data for nerve and muscle electrodes. Peak twitch tension is monitored over the range from threshold to maximal stimulation. Either pulse amplitude or duration can be selected as the variable stimulus parameter. The system uses three key subroutines: one to measure maximum twitch tension, a second to determine the appropriate points at which tension should be measured, and a third to generate the estimated recruitment curve. >

Investigation of the mechanisms of muscle adaptation requires independent control of the regulating factors. The aim of the present study was to develop a serum-free medium to culture mature single muscle fibres of Xenopus laevis. As an example, we used the culture system to study adaptation of twitch and tetanic force characteristics, number of sarcomeres in series and fibre cross-section. Fibres dissected from m. iliofibularis (n = 10) were kept in culture at a fibre mean sarcomere length of 2.3 microm in a culture medium without serum. Twitch and tetanic tension were determined daily. Before and after culture the number of sarcomeres was determined by laser diffraction and fibre cross-sectional area (CSA) was determined by microscopy. For five fibres twitch tension increased during culture and tetanic tension was stable for periods varying from 8 to 14 days ('stable fibres'), after which fibres were removed from culture for analysis. Fibre CSA and the number of sarcomeres in series remained constant during culture. Five other fibres showed a substantial reduction in twitch and tetanic tension within the first five days of culture ('unstable fibres'). After 7-9 days of culture, three of these fibres died. For two of the unstable fibres, after the substantial force reduction, twitch and tetanic tension increased again. Finally at day 14 and 18 of culture, respectively, the tensions attained values higher than their original values. For stable fibres, twitch contraction time, twitch half-relaxation time and tetanus 10%-relaxation time increased during culture. For unstable fibres these parameters fluctuated. For all fibres the stimulus threshold fluctuated during the first two days, and then remained constant, even for the fibres that were cultured for at least two weeks. It is concluded that the present culture system for mature muscle fibres allows long-term studies within a well-defined medium. Unfortunately, initial tetanic and twitch force are poor predictors of the long-term behaviour of the fibres.

The purpose of this study was to investigate the effects of hindlimb suspension (HS) on contractile properties of skeletal muscles of young and old rats and to determine the impact of electrical stimulation (ES) on the quality and degree of recovery of these muscles. After 21 days of HS, young soleus (SOL) muscle became faster, but there was no impact on young extensor digitorum longus (EDL) muscle. Twitch tension (Pt) decreased 61% in young and 70% in old SOL muscles. Specific tetanic tension (Po) decreased 53% in young and 64% in old SOL muscles, but again there was no impact on EDL muscle. After a 14-day period of recovery, contraction time (CT), half-relaxation time (RT1/2), Pt and Po returned to control group values in both young and old SOL muscles. Measurements of the contractile properties of young and old skeletal rat muscles showed ES sometimes to be beneficial but also sometimes to be harmful. A 14-day period of recovery, with or without ES, seemed sufficient for many variables to return to control group values.

Publisher Summary This chapter discusses the effects of pressure on shallow-water fishes. The measurements of the concentrations of various substances in organs and/ or tissues are generally performed on tissue samples taken from fishes that are first exposed to high pressure and then decompressed. It is observed that when isolated muscle is pressurized, an increase in maximum twitch tension and in the time taken to reach peak tension is noted. It is found that when isolated gill preparations are incubated in artificial seawater and then submitted to hydrostatic pressure, various changes occur in tissue Na + , K + , and Cl - contents, depending on the experimental pressure. Na + content varies much more rapidly than CI - and K + . In shallow-water fishes exposed to the pressures of about 50–100 ATA, changes in ion contents are principally because of changes in permeability and not to changes in active transport. The effects are mainly an increase in Na + content and a decrease in K + content. The information provided in the chapter shows that a shallow-water fish is able to acclimatize to high pressure and that during this acclimatization physiological changes occur that makes the fishes less sensitive to further compression. The acclimatization of trout and goldfish for at least 21 days at 101 ATA has also been successful, provided that care was taken to compress the fish slowly.

Effects of increased hydrostatic pressure (range 0.1-10 MPa) on isometric twitch and tetanic contractions of single, intact, frog muscle fibres were examined at 4, 11 and 21 degrees C and at different stages of fatigue. Twitch tension was potentiated by pressure at all temperatures, but the extent of potentiation was more pronounced at higher temperatures (34% MPa-1 at 21 degrees C, compared to 8% MPa-1 at 4 degrees C). Tetanic tension was depressed by pressure at 4 degrees C (approximately 0.7% MPa-1) but was potentiated by pressure at 21 degrees C (approximately 0.4% MPa-1). The effect of hydrostatic pressure on the tetanic tension was dependent on the fatigue status of the muscle fibre: during the early stages of fatigue (when tetanic tension was depressed by < 20%), high pressure produced a tension depression (as in an unfatigued muscle fibre), whilst during the later stages of fatigue high pressure induced a significant potentiation of tetanic. Our results support the suggestion that excitation-contraction coupling and contractile activation are impaired during late fatigue. Pressure-effects were basically similar to caffeine-effects under a variety of conditions, suggesting that an enhancement of Ca2+ release may be contributory to potentiation of twitch tension and, in severely, fatigued muscle, potentiation of tetanic tension. In the rested state and during early fatigue the main effect of pressure is an inhibition of the crossbridge cycle.

The study was planned to compare the sensitivity of a twitch neuromuscular monitoring test, the train-of-four (TOF), with a tetanic test, double-burst stimulation (DBS), during a subclinical dose of vecuronium. Twenty consenting. ASA I patients (16 to 65 years of age) of both sexes were studied. The ulnar nerve was stimulated at the wrist through surface electrodes by Myotest-DBS, and the adductor pollicis response was recorded on Myograph-2000. After stabilization of the twitch tension at titrated supramaximal stimuli (1 Hz), patients were randomly allocated into groups. In group 1 (n=10), the TOF test was monitored; in group 2 (n=10), the DBS test was monitoral. All patients received a priming dose of vecuronium (0.015 mg·kg−1); parameters such asT 1 and TOF ratio (TOFr) (T 4/T 1) were noted in group 1, andD 1 and DBS ratio (DBSr) (D 2/D 1) were noted during the vecuronium effect. The DBS test showed a wider range of change (from control 1.00 to 0.62±0.19 forD 1 and to 0.37±0.14 for DBSr) at a faster rate (0.07±0.04 min−1 forD 1 and 0.08±0.02 min−1 for DBSr) during the block progression phase than the TOF test parameters (T 1 and TOFr). The tetanic fade or DBSr showed peak onset later than peak twitch suppression. The rate of recovery of the DBS test was also slower than that of the TOF test after the peak effect. DBS is a more sensitive test than TOF to quantify the subclinical dose effect of vecuronium, and among the studied parameters (T 1, TOFr,D 1 and DBSr), DBSr, measuring tetanic fade, was the most sensitive single parameter.

The effect of H2O2 was examined to elucidate the basis of muscle injury after exercise. Exposure of single fibers to 1.5-6 mM H2O2 led to twitch potentiation followed by a marked decrease. Then, fibers contracted spontaneously. BAY K 8644 augmented twitch potentiation and slowed the decay of twitches. In 5 mM dithiothreitol (DTT), twitch potentiation and spontaneous contraction were not observed on H2O2 addition. Cytoplasmic application of 1.5-3 mM H2O2 to heavy sarcoplasmic reticulum (SR) vesicles incorporated into planar lipid bilayers increased the open probability of Ca2+ release channels, an effect reversed by DTT. We investigated oxidation of sulfhydryl groups on proteins in SR membrane by H2O2 with N-(7-dimethylamino-4-methyl-3-coumarinyl)maleimide. Pretreatment of light and heavy SR membranes with 1.5 mM H2O2 exponentially increased fluorescence intensity. The time constant of the intensity increase was increased markedly only in heavy SR in solution containing 50 microM cytoplasmic Ca2+, so Ca2+ release was associated with protein oxidation by H2O2. Thus extracellular H2O2 probably acts by oxidizing sulfhydryls of proteins at two distinct sites: the dihydropyridine receptors, oxidation of which elicits potentiation and subsequent inhibition of twitches, and Ca2+ release channels, whose oxidation elicits spontaneous contraction, resulting in muscle dysfunction.

We studied the effect of aminophylline (1 mM) and 9-aminoacridine (100 μM) on the contraction threshold (CT) of rat diaphragm fibers (25 °C) . The CT was measured by direct visualization (200 X) of the fiber under current-clamp conditions. The main findings are the following: 1) Aminophylline lowers the CT toward more negative values of the resting membrane potential (V m ). 2) 9-aminoacridine, a drug that diminishes Ca 2+ release from the sarcoplasmic reticulum (SR), shifts the CT toward more positive values; 3) this effect is overcome by aminophylline. We suggest that the displacement in the CT to more negative V m plays an important role in the potentiating effect of aminophylline. This could be the result of an enhancement of Ca 2+ release from the SR.

Objective: To study the influence of hypothermic cardiopulmonary bypass (CPB) on the pharmacodynamics and pharmacokinetics of rocuronium. Design: Prospective, descriptive study. Setting: Operating room at a university hospital. Participants: Ten ASA class III end IV patients, ranging in age from 35 to 75 years, scheduled for elective coronary artery bypass grafting. Interventions: Neuromuscular transmission was monitored mechanomyographically. The time course of action of maintenance doses and plasma concentration-response relationships were determined before, during, and after OPE. The plasma concentration decay and renal elimination were studied simultaneously. Plasma and urine concentration of rocuronium ware determined by high-performance liquid chromatography. Measurements and Main Results: Hypothermic CPB prolonged the duration of action of coincided with a lower plasma concentration at a twitch response of 5% of control. The duration of action of maintenance doses returned to prehypothermic CPB level after rewarming to a nasopharyngeal temperature of 37 degrees C. The plasma concentration-response relationship did not return to precooling control value, probably owing to persisting peripheral hypothermia. Both the renal elimination of rocuronium and the plasma concentration decay after the last maintenance dose under normothermic conditions resembled values obtained in patients not undergoing hypothermic CPB. Conclusions: Hypothermic CPB prolongs the duration of action of maintenance doses and alters the plasma concentration-response relationship of rocuronium. These changes may be the result of, on the one hand, an increased sensitivity of the neuromuscular transmission and/or decreased muscle contractility and, on the other hand, the result of a reduced plasma clearance during hypothermia. (C) 1995 by W.B. Saunders Company

In adult mammalian skeletal muscles, fast and slow muscle fibers are selectively innervated by single inputs from corresponding motor neuron types, giving rise to fast and slow motor units. At birth, however, muscle fibers are polyinnervated, and connections between motor neurons and muscle fibers are not as specific as those found in adults. Excess synapses are removed during the first few postnatal weeks. In addition to changes in the degree of polyinnervation, motor unit types undergo maturation in their contractile properties. In this study, we have investigated the maturation of motor unit types during postnatal synapse elimination in the rabbit soleus muscle. The ratio of twitch tension to tetanic tension in a motor unit is an indication of its contractile type. Our results indicate that during synapse elimination, the twitch/tetanus ratios for fast motor units increase while those for slow motor units decrease. The ratio of motor unit tension at polyinnervated ages to that at singly innervated ages has previously been used to estimate the degree of polyinnervation for fast versus slow muscle fibers. We found that twitch and tetanic tension yield conflicting estimates of polyinnervation. This discrepancy was resolved on the basis of intracellular recordings of endplate potentials. Using latencies to endplate potentials as an indicator of muscle fiber type, we found that fast and slow muscle fibers are polyinnervated to a similar extent during both early and intermediate stages of synapse elimination, suggesting that specific tension, and not polyinnervation, changes differently in fast versus slow muscle fibers. These changes ate consistent with those we found in twitch/tetanus ratios. Furthermore, these intracellular recordings suggest a high degree of specificity at birth, which is further refined during synapse elimination.

Although mivacurium is eliminated by plasma cholinesterase, previous investigations have revealed either no relationship or limited correlation between mivacurium infusion rates (IRs) and plasma cholinesterase activity. Assuming that such a relationship should exist, we used a novel approach to better demonstrate the relationship in humans. Fourteen isoflurane-anesthetized adults underwent standard neuromuscular monitoring. Mivacurium was then infused at 1.0 micrograms.kg-1.min-1 until twitch tension stabilized. The IR was then adjusted, using the Hill equation, to produce approximately steady state 50% (n = 14) or 90% (n = 13) twitch depression. Using these values for IR and steady-state twitch depression, the IRs expected to produce 50% and 90% twitch depression (IR50 and IR90, respectively) were estimated by on nonlinear regression. Both IR50 (r2 = 0.51, P < 0.005) and IR90 (r2 = 0.48, P < 0.01) were related to plasma cholinesterase activity; the coefficient of the Hill equation did not vary with plasma cholinesterase activity. We conclude that mivacurium IRs are, as expected, influenced by the activity of the enzyme responsible for its elimination.

Previously, the effect of hypothermia on muscle twitch tension in the presence and absence of neuromuscular blocking drugs has been studied several times. It is striking that few clinical studies have been done previously. Because almost all investigations have been performed within a temperature range not normally encountered clinically, it is unclear if previously obtained results are applicable to every-day anesthesia. Previous results are conflicting. Additionally, the adductor pollicis muscle temperature has not been recorded during cooling.