Single Twitch Tension Research Articles

Determining the effect of long-term dexamethasone and prednisolone treatment on sugammadex

Background/aim: We aimed to investigate the effect of long-term use of dexamethasone and prednisolone on the reversal effect of sugammadex. Materials and methods: TTwenty-four male Wistar albino rats were divided into three groups. Dexamethasone (600 µg/kg) was given to group D, prednisolone (10 mg/kg) was given to group P, and an equivalent volume of saline per day was administered intraperitoneally to group S for 14 days, respectively. The left hemidiaphragm with attached phrenic nerve was maintained in Krebs solution. Sugammadex (30 µmol/L) was applied while rocuronium (10 µmol/L) was present in an organ bath and a single twitch was obtained. The right hemidiaphragm was used for both adult ( ε-subunit) and fetal nicotinic acetylcholine receptor (AChR) ( ε-subunit) determination using polymerase chain reaction. Results: All animals lost weight, except group S. The mean baseline single-twitch tension was lower in both group D (14.4 ± 1.7 g) and group P (12.68 ± 0.05 g) than group S (16.8 ± 0.5 g) (P < 0.001). When sugammadex was added to the organ bath while rocuronium was present, the single twitch was measured to be lower in both group D (11.7 ± 0.7 g) and group P (11.5 ± 0.78 g) than group S (16.5 ± 0.24 g) (P < 0.001). Ɣ-AChR expression was higher in both dexamethasone and prednisolone than in saline. Conclusion: Long-term medication with dexamethasone and prednisolone caused muscle weakness, resistance to neuromuscular blockers, and upregulation of immature Ɣ-AChR and reduced the neuromuscular reversal effect of sugammadex.

The effect of high concentration of magnesium with ropivacaine, gentamicin, rocuronium, and their combination on neuromuscular blockade.

BackgroundMagnesium, ropivacaine, gentamicin, and rocuronium block neuromuscular (NM) transmission by different mechanisms. Therefore, concurrent administration of these agents may induce prolonged muscle paralysis via synergistic interaction. This study investigated the efficacy and safety of NM block caused by the administration of high concentrations of magnesium in combination with ropivacaine, gentamicin, and rocuronium.MethodsEighty-three left phrenic nerve-hemidiaphragms from male SD rats (150-250 g) were hung in Krebs solution. Three consecutive single twitch tension (ST, 0.1 Hz) and one tetanic tension (TT, 50 Hz for 1.9 s) were obtained before drug application and at each new drug concentration. The concentration of MgCl2 and MgSO4 in Krebs solution was increased until an 80 to 90% reduction in ST was reached. To test the effects of combinations of NM agents, a Krebs solution was premixed with MgCl2 alone, MgCl2 and ropivacaine, or MgCl2, ropivacaine, and gentamicin. The concentration of ropivacaine, gentamicin, or rocuronium was then progressively increased until an 80 to 90% reduction in ST was reached. The effective concentrations were estimated with a probit model.ResultsThe potency of MgCl2 was greater than that of MgSO4, and pretreatment with MgCl2 increased the potency of gentamicin and rocuronium. Unexpectedly, MgCl2 did not potentiate ropivacaine, and the potency of gentamicin and rocuronium failed to show an increase when premixed with 0.5 µM ropivacaine.ConclusionsThe concomitant administration of high concentrations of magnesium and ropivacaine together with clinically relevant concentrations of gentamicin or rocuronium potentiated NM blockade but not with clinically relevant concentrations of ropivacaine.

The synergistic effect of gentamicin and clindamycin on rocuronium-induced neuromuscular blockade

BackgroundGentamicin 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.MethodsMale 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.ResultsThe 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.ConclusionsThis study demonstrate that gentamicin and clindamycin potentiated rocuronium induced neuromuscular blockade. Moreover, it was found that these drugs interacted synergistically.

Effect of 5-day vitamin E supplementation on muscle injury after downhill running in rats

Antioxidant supplementation has been suggested to prevent exercise-induced muscle injury, but the findings are inconsistent. The objective of this study was to investigate the potential protective role of vitamin E treatment against eccentric exercise-induced muscle injury by examining morphological and functional alterations in rat soleus muscle after downhill running as well as muscle injury markers in the blood. Sixty adult male Wistar rats were randomly assigned to vitamin E-treated or placebo-treated groups studied at rest, immediately post-exercise or 48h post-exercise (n=10 per group). Vitamin E was administered by daily intraperitoneal injections of 100mg/kg body mass of DL: -α-tocopheryl acetate for five consecutive days prior to exercise, resulting in the doubling of its plasma concentration. Downhill running resulted in significant (P<0.05) changes in all injury markers for the placebo-treated rats at 0 and 48h post-exercise. However, significantly smaller soleus muscle single-twitch tension (P (t)) and unfused (40Hz) tetanic force, and greater plasma creatine kinase (CK) and lactate dehydrogenase (LD) activities compared with the control were found only immediately post-exercise for the vitamin E-treated rats (P<0.05). Maximal tetanic force (P (o)) did not decline significantly compared to sedentary controls at neither time points measured. The vitamin E-treated rats had significantly (P<0.05) higher soleus muscle P (t) immediately post-exercise than the placebo-treated rats as well as lower plasma CK and LD activity 48h post-exercise. However, there was no difference in P (o) decline between groups at either time points measured. Vitamin E-treated rats had less pronounced morphological alterations in muscle in the immediate and 48-h post-exercise period. In conclusion, the effect of short-term vitamin E supplementation against eccentric exercise-induced muscle injury did not appear to be physiologically significant, because vitamin E failed to prevent the decline in the functional measure of P (o) compared to the placebo conditions.

The role of ascorbic acid and exercise in chronic ischemia of skeletal muscle in rats

This study was designed to investigate the effects of peripheral arterial insufficiency, exercise, and vitamin C administration on muscle performance, cross-sectional area, and ultrastructural morphology in extensor digitorum longus (EDL) and soleus (Sol) muscles in rats. Adult Wistar rats were assigned to ischemia alone (isch), ischemia-exercised (exe), ischemia-vitamin C (vit C), and ischemia-exercise-vitamin C (vit C + exe) groups. Ischemia was achieved via unilateral ligation of the right common iliac artery. Contralateral muscles within the same animal served as controls. Exercise protocol consisted of 50-min intermittent level running performed every other day for 5 days. Vitamin C (100 mg/kg body wt) was administered intraperitoneally on a daily basis throughout the 14 days of the experiment. With regard to the EDL muscle, ischemia alone reduced muscle strength, which was not recovered after vitamin C administration. Exercise alone following ischemia induced the most severe structural damage and cross-sectional area decrease in the muscle, yet the reduction in tetanic tension was not significant. Exercise in conjunction with vitamin C administration preserved ischemia-induced EDL muscle tetanic tension. In the Sol muscle, a significant reduction in single twitch tension after vitamin C administration was found, whereas the tetanic force of the ischemic Sol was not significantly decreased compared with the contralateral muscles in any group. Ischemic Sol muscle cross-sectional area was reduced in all but the exe groups. In Sol, muscle strength was reduced in the vit C group, and mean cross-sectional area of ischemic Sol muscles was reduced in all groups except the exe group. These results illustrate that mild exercise, combined with a low dose of vitamin C supplementation, may have beneficial effects on ischemic EDL muscle with a smaller effect on the Sol muscle.

The Effect of Nicorandil on the Pharmacodynamics of Rocuronium

Background: Some investigators have shown that nicorandil, a KATP channel opener, depresses the neuromuscular transmission contraction of the skeletal muscle. However, others have reported that it improves the recovery of vecuronium relaxation and the myotonic activity of muscle. This study investigated the effect of nicorandil on rocuronium relaxation. Methods: Hemidiaphragm-phrenic nerve preparations were obtained from male Sprague-Dawley rats (150-250 g). The preparations were bathed in Krebs' solution containing in (mM): NaCl 118, KCl 5, 2.5, 30, 1, 1 and glucose 11. The preparations were, then maintained at 32 and aerated with a mixture of 95% and 5% . Isometric forces that were generated in response to 0.1 Hz, and, 50 Hz for 1.9 seconds with supramaximal electrical stimulation (0.2 msec, rectangular) to the phrenic nerve were measured using a force transducer. The single twitch tension (ST) and peak tetanic tension (PTT) were calculated as % inhibition of the control, and the tetanic fade (TF), as % increase in the PTT. Each preparation was exposed to one of the 6 nicorandil concentrations (0.0, 0.625, 1.25, 2.5, 5, 10), and the adequate volume of the rocuronium solution was cumulatively added to the tissue bath for a desired rocuronium concentration until there was an 80-90% decrease in the ST. The effect of rocuronium at each concentration was allowed to reach a steady state before the tension parameters were measured. The , , 0, , and of rocuronium for the ST, PTT and TF were calculated using a probit model. The differences between the 0 of rocuronium according to the nicorandil concentrations were tested using a t-test and a Bonferroni's correction. Results: 1.25 and 2.5 nicorandil shifted the cumulative concentration-response curves for the TF of rocuronium to the right. 5 and 10 nicorandil shifted the cumulative concentration-response curves for the ST of rocuronium to the left. Conclusions: Lower concentration of nicorandil may help maintain the tetanic contraction during rocuronium relaxation

The Effect of Kanamycin on Rocuronium Neuromuscular Blockade in Rat Hemidiaphragm-phrenic Nerve Preparations

Background: Kanamycin has been shown to block neuromuscular transmission by reducing acetylcholine can release or blocking postsynaptic receptors. This study was undertaken to investigate whether kanamycin can potentiate rocuronium neuromuscular block. Methods: Hemidiaphragm-phrenic nerve preparations were obtained from male Sprague-Dawley rats (150-250 g). Preparations were bathed in Kreb's solution of (mM): NaCl 118, KCl 5, 2.5, 30, 1, 1 and glucose 11 maintained at and aerated with a mixture of 95% and 5% . Isometric forces generated in response to 0.1 Hz and 50 Hz for 1.9 seconds with supramaximal electrical stimulation (0.2 msec, rectangular) to the phrenic nerve, were measured using a force transducer. The effects of drugs on single twitch tension (ST) and peak tetanic tension (PTT) were calculated as % inhibition of control and tetanic fade (TF), as % increase. Each preparation (n = 20) was exposed to one of 4 kanamycin concentrations (0.0, 1.0, 2.0, 4.0 mM), and an adequate volume of rocuronium solution was cumulatively added to the tissue bath to achieve a 80-90% reduction in ST. An adequate volume of kanamycin solution was cumulatively added to the other 5 preparations to achieve a 80 90% reduction in ST. The effect of kanamycin or rocuronium at each concentration was allowed to reach a steady state before tension parameters were measured. , , , , and of rocuronium and kanamycin for ST, PTT and TF were calculated using a probit model. Drug interactions were drawn using Berenbaum´s additive isobole at 25% isobole, 50% isobole, and 75% isobole. Differences between ´s of rocuronium at different kanamycin concentrations were tested using one way ANOVA with Tamhane post hoc analysis, P values of ＜ 0.05 were regarded significant. Results: Kanamycin shifted cumulative concentration-response curves to the right. The interactions of these drugs varied from additive to antagonistic or synergistic according to the magnitude of neuromuscular block, concentration of the drugs and the frequency of the stimulation. Conclusions: Kanamycin lowered the effective concentration of rocuronium, but the interaction between rocuronium and kanamycin was variable.

The Effect of Magnesium on the Verapamil Neuromuscular Blockade in Rat Phrenic Nerve-Hemidiaphragm Preparations

Background: At the neuromuscular junction, magnesium acts on the release of acetylcholine and on the excitability of sarcolemma. Verapamil inhibits acetylcholine release and enhances the autodesensitization of acetylcholine receptor ion channels. So, we studied the effect of magnesium on the neuromuscular blocking action of verapamil. Methods: Hemidiaphragm-phrenic nerve preparations were obtained from male Sprague-Dawley rats (200-300 g). Preparations were bathed in Kreb's solution of (mM): NaCl 118, KCl 5, 2.5, 30, 1, 1 and glucose 11, then maintained at , and aerated with a mixture of 95% and 5% . Isometric forces generated in response to 0.1 Hz and 50 Hz for 1.9 seconds with supramaximal electrical stimulation (0.2 msec, rectangular) to the phrenic nerve, were measured with a force transducer. Single twitch tension (ST) and peak tetanic tension (PTT) were calculated as % reduction versus the control, and tetanic fade (TF) as a % increase. Each preparation was exposed to one of 4 magnesium concentrations of Krebs' solution (0.5, 1.0, 2.0, 3.0 [mM]), and the adequate volume of verapamil stock solution was added to the tissue bath to achieve the desired verapamil concentration. The effects of magnesium and verapamil were allowed to reach a steady state before tension parameters were measured. of verapamil for ST, PTT and TF were calculated using a probit model. Differences between the 's of verapamil according to magnesium concentrations were tested using the Mann-Whitney U test with the Bonferroni correction, P

The Effect of Pefloxacin on Rocuronium-Induced Neuromuscular Blockade in Rat Phrenic Nerve-Hemidiaphragm Preparations

Background: At the neuromuscular junction, pefloxacin (P) may exacerbate myasthenia gravis and reduce the tau of MEPC. So here we investigated the effect of P on the neuromuscular blocking action of rocuronium (R). Methods: Hemidiaphragm-phrenic nerve preparations were obtained from male Sprague-Dawley rats (150-250 g). Preparations were bathed in Kreb's solution (in (mM): NaCl 118, KCl 5, 2.5, 30, 1, 1 and glucose 11), maintained at and then aerated with a mixture of 95% O2 and 5% CO2. Isometric forces generated in response to 0.1 Hz, and, 50Hz for 1.9 seconds with supramaximal electrical stimulation(0.2 msec, rectangular) to the phrenic nerve, were measured with a force transducer. Single twitch tension (ST) and peak tetanic tension (PTT) were calculated as % reduction versus the control, and tetanic fade (TF), as a % increase. Each preparation was exposed to one of 4 P concentrations of Krebs' solution (0, 0.25,0.5, 1.0 mM), and enough R solution was added to the tissue bath to achieve the desired R concentration. The effects of P and R were allowed to stabilize before measuring tension parameters. , , , , and of R for ST, PTT and TF were calculated using a probit model. The interactions between the two drugs were drawn with Berenbaum's additive isobole at 25% isobole, 50% isobole, and 75% isobole. Differences between EC50's of R according to P concentrations were tested by one way ANOVA with Tamhane for post hoc; P

Extraocular muscle force generation after ricin-mAb35 injection: implications for strabismus treatment.

Ricin-mAb35 is an immunotoxin targeted against skeletal muscle. Previously, we have shown that injection of ricin-mAb35 into rabbit extraocular muscle results in long-term muscle loss, and we have proposed this as a potential treatment for strabismus. In this study, we assessed the effects of ricin-mAb35 injection on extraocular muscle force generation. Ricin-mAb35, 0.2 microg/kg in a volume of 0.1 mL, was injected into 1 superior rectus muscle in 16 adult rabbits. The contralateral superior rectus was injected with an equal volume of normal saline. Muscle force generation was assessed in vivo at 1, 6, and 12 weeks. Isometric length-tension curves were developed. Single-twitch tension, peak tetanic force generation, and fatigue rate were determined at optimal preload. Data from treated and control muscles were compared with the paired t test. Force generation declined in ricin-mAb35 treated muscles at each postinjection interval. At 12 weeks, mean tetanic tension (200 Hz) in treated muscles was 13.8 mN/cm(3) compared with 27.7 mN/cm(3) in saline-injected controls (P =.02), a reduction of 50%. Single-twitch tension at 12 weeks was reduced 33% compared to controls (P =.04). Similar effects were noted at 1 and 6 weeks. Fatigue rate was not greater in treated muscles at any postinjection intervals. Injection of ricin-mAb35 results in sustained weakness in extraocular muscle, although additional studies will be required to determine the duration of physiologic effect. These results confirm our histological analysis and suggest that ricin-mAb35 may be a more long-term alternative to botulinum toxin A for the treatment of strabismus.

Extraocular muscle force generation after ricin-mAb35 injection: implications for strabismus treatment

Purpose Ricin-mAb35 is an immunotoxin targeted against skeletal muscle. Previously, we have shown that injection of ricin-mAb35 into rabbit extraocular muscle results in long-term muscle loss, and we have proposed this as a potential treatment for strabismus. In this study, we assessed the effects of ricin-mAb35 injection on extraocular muscle force generation. Methods Ricin-mAb35, 0.2 μg/kg in a volume of 0.1 mL, was injected into 1 superior rectus muscle in 16 adult rabbits. The contralateral superior rectus was injected with an equal volume of normal saline. Muscle force generation was assessed in vivo at 1, 6, and 12 weeks. Isometric length-tension curves were developed. Single-twitch tension, peak tetanic force generation, and fatigue rate were determined at optimal preload. Data from treated and control muscles were compared with the paired t test. Results Force generation declined in ricin-mAb35 treated muscles at each postinjection interval. At 12 weeks, mean tetanic tension (200 Hz) in treated muscles was 13.8 mN/cm 3 compared with 27.7 mN/cm 3 in saline-injected controls ( P = .02), a reduction of 50%. Single-twitch tension at 12 weeks was reduced 33% compared to controls ( P = .04). Similar effects were noted at 1 and 6 weeks. Fatigue rate was not greater in treated muscles at any postinjection intervals. Conclusions Injection of ricin-mAb35 results in sustained weakness in extraocular muscle, although additional studies will be required to determine the duration of physiologic effect. These results confirm our histological analysis and suggest that ricin-mAb35 may be a more long-term alternative to botulinum toxin A for the treatment of strabismus.

Neuromuscular Blocking Actions and Mechanisms of Kanamycin, Pefloxacin and Rocuronium in the Rat Phrenic Nerve-Hemidiaphragm Preparations

Background: Kanamycin (K) has been shown to block neuromuscular transmission by reducing acetylcholine release or postsynaptic action. Pefloxacin (P) may exacerbate myasthenia gravis and reduce the tau of MEPP. Rocuronium (R) is still the subject of dispute as to whether it has a selective presynaptic effect. Therefore, we undertook to compare the muscle relaxation actions and reversibilities of K, P and R. Methods: Hemidiaphragm-phrenic nerve preparations were obtained from male Sprague-Dawley rats (150-250 g). Preparations were bathed in Krebs' solution ([mM]: NaCl 118, KCl 5, 2.5, 30, 1, 1 and glucose 11), maintained at and aerated with a mixture of 95% and 5% . Isometric forces generated in response to 0.1 Hz, and 50 Hz for 1.9 seconds with supramaximal stimulation (0.2 ms, rectangular) to the phrenic nerve, were measured using a force transducer. The effects on single twitch tension (ST) and peak tetanic tension (PTT) were calculated as % reduction. The effects on tetanic fade (TF) were calculated as % increase. K, P and R were added to the tissue bath to achieve the desired bath concentrations. , , , , and for ST, PTT and TF were calculated using a probit model. The antagonism indices of neuromuscular blockades by calcium (5 mM), 3,4-diaminopyridine (3,4-DAP) (10M), and neostigmine (N) (250 nM) were assessed at 85 5% reduction (or increase). Results: The potencies of ST, PTT and TF were 5.49, 5.73 and 6.30 (mM) for K, 1.90, 1.67 and 1.31 (mM) for P, and 10.81, 5.27 and 4.41 (M) for R. The correlation between ST, PTT and TF varied for K, P and R. Neuromuscular blockades of K were reversed similarly by calcium and 3,4-DAP, and partially by N, whilst those of P were not, and ST reduction of R was reversed by 3,4-DAP (98%) and PTT and TF of R were partially reversed by 3,4-DAP and N. Conclusions: It is considered probable that K inhibits acetylcholine release and noncompetitively blocks postsynaptic sites, P postsynaptically depresses the neuromuscular transmission with acetylcholine receptor-ion channel block and that R has not only a selective presynaptic effect but also a postsynaptic block effect.

Muscle contractility decrement and correlated morphology during the pathogenesis of streptozotocin-diabetic mice.

Peripheral neuropathy of both motor and sensory nerves has been well documented in diabetes mellitus, but the evidence for physiological and correlated morphological changes during the pathogenesis of myopathy is scarce. In the present report, we have chosen the dorsiflexor muscle of adult male mice as a model for studying in situ muscle contraction and neuromuscular ultrastructure during the pathogenesis of streptozotocin-induced diabetes. Thirty mice (30 g bodyweight) were injected once i.p. with streptozotocin solution (200 mg/Kg) to induce experimental diabetes mellitus. Comparative analyses of in situ muscle isometric contractile characteristics were studied (at 1 Hz, 5 Hz and 30 Hz nerve stimulation) in urethane-anesthetized (2 mg/g, i.p.) control and diabetic mice at three time points, 2 weeks, 4 weeks, and 8 weeks postinjection. Synaptic delay was also recorded in diabetic and age-matched control mice. There was a significant increase in synaptic delay in both 4-week and 8-week diabetic mice compared with control mice (8.9 +/- 1.2 msec and 7.6 +/- 0.6 msec, respectively, compared with 6.1 +/- 0.5 msec). At all three stimulation frequencies, diabetes did not affect muscle contractile speed but significantly reduced the twitch tension after 8 weeks, with no changes at 2 weeks or 4 weeks. The recorded single-twitch tension values were 2.6 +/- 0.3 g, 2.1 +/- 0.6 g, 2.2 +/- 0.7 g, and 1.2 +/- 0.1 g for control, 2 weeks, 4 weeks, and 8 weeks, respectively. At 30 Hz, the recorded tension values were 4.6 +/- 1.6 g, 3.1 +/- 1.2 g, 3.1 +/- 1.1 g, and 2.1 +/- 1.0 g for control, 2 weeks, 4 weeks, and 8 weeks, respectively. Ultrastructural changes in neuromuscular junctions were similar to those that have been described in disuse and aging. These changes were observed after 8 weeks and included serve loss of synaptic vesicles, electron-dense bodies, and myelin-like figures as well as degeneration of mitochondria. The results reveal that streptozotocin-induced diabetes affects presynaptically the neuromuscular junction as well as muscle itself. Actions at both sites may contribute to the functional alterations seen in muscle contractile properties and may play a role in the pathogenesis of diabetic neuromyopathy.

Twitch/tetanus ratio and its relation to other properties of motor units.

The ratio of single twitch tension to maximal tetanic tension (Tw/Tet ratio) represents one of the physiological properties of single motor units. In our study, in agreement with the results of other studies, the mean Tw/Tet ratio of slow motor units was lower than that of fast motor units. But we found that the Tw/Tet ratios of the slow motor units with twitch tension between 0.75 and 1.5 g were higher than those of fast motor units with twitch tension in the same range. A significant linear relation between Tw/Tet ratio and twitch tension was obtained for the three types of motor units. This relationship could be due to the increasing number of muscle fibres within a motor unit with the twitch tension.

Impaired neuromuscular transmission during partial inhibition of acetylcholinesterase: the role of stimulus-induced antidromic backfiring in the generation of the decrement-increment phenomenon.

Neuromuscular transmission was studied in the rat phrenic nerve-hemidiaphragm preparation with acetylcholinesterase (AChE) partially inactivated. Enzyme inhibition resulted in (1) increased single-twitch tension of the diaphragm; (2) compound muscle action potential (CMAP) containing repetitive discharges; (3) stimulus-induced antidromic backfiring (SIAB) seen in the phrenic nerve; and (4) repetitive nerve stimulation (RNS) eliciting a decrement-increment (D-I) phenomenon (i.e., amplitude reduction maximal with the second CMAP). Using a high-calcium and low-magnesium solution, SIAB and the decrement of the second CMAP during RNS were intensified, whereas closely spaced trains and (+)-tubocurarine (TC) abolished SIAB and simultaneously prevented the decrement of the second CMAP. Importantly, low concentrations of (+)-TC prevented SIAB in the phrenic nerve, while the repetitive discharges of the CMAP and the increase in twitch tension remained unaffected. This observation suggests that preterminal nicotinic receptors stimulated by released acetylcholine induce SIAB, whereas postsynaptic events are less important in the generation of SIAB. SIAB, a presynaptic event, appears to be responsible for the transient impairment of the neuromuscular transmission, i.e., the D-I phenomenon.

Edrophonium antagonizes combined lidocaine-pancuronium and verapamil-pancuronium neuromuscular blockade in cats.

The effects of lidocaine or verapamil on pancuronium neuromuscular blockade and the ability of anticholinesterase agents to antagonize these combined blockades were studied in 14 cats using a standard peroneal nerve-anterior tibialis muscle preparation. Pancuronium was infused at a constant rate to produce a stable 50% depression of single twitch tension. In nine cats, intravenous lidocaine boluses followed by a constant infusion produced serum lidocaine levels of 5.09 +/- 1.9 micrograms/ml (mean +/- SD) and resulted in an additional 20.0 +/- 5.5% depression of twitch tension. In the other five cats, intravenous injection of 0.15 mg/kg of verapamil produced an additional 12.8 +/- 8.0% twitch depression of pancuronium-induced neuromuscular blockade. For individual animals, edrophonium antagonism of the combined lidocaine-pancuronium-induced neuromuscular blockade or combined verapamil-pancuronium-induced neuromuscular blockade was not significantly different from antagonism of an equivalent twitch depression produced by pancuronium alone. It is concluded that lidocaine and verapamil augment neuromuscular blockade caused by pancuronium and that anticholinesterase antagonism of this augmented blockade can be expected to occur in a normal fashion.

Refining the priming principle for vecuronium during rapid-sequence induction of anesthesia.

Administration of a subparalyzing dose of a nondepolarizing muscle relaxant (priming dose) prior to its intubating dose hastens the onset time (time from muscle relaxant administration to 100% depression of twitch tension) of neuromuscular blockade. This study was undertaken to determine the optimal priming and intubating doses and time interval between these doses (priming interval) of vecuronium during rapid-sequence induction of anesthesia. The authors measured single-twitch tension in 79 healthy, awake, premedicated (fentanyl, 50-150 mu iv, and/or diazepam, 5-10 mg iv) patients. In Part A of the study, the priming dose was varied (0.0, 0.005, 0.01, 0.0015, or 0.02 mg/kg iv). Decrement of twitch tension and symptoms were recorded 3 min later. Four minutes after the priming dose, thiopental, 4-6 mg/kg iv, and vecuronium, 0.1 mg/kg iv, were given. Onset times for the 0.01, 0.015, and 0.02 mg/kg groups were significantly shorter than for 0.005 and 0.0 mg/kg groups. No breathing difficulties were encountered in any of the groups. Decrement of twitch tension greater than 25% of control only occurred in the 0.02 mg/kg group (4 of 11 patients). In Part B, the priming interval was varied (2, 4, or 6 min) after giving the optimal priming dose (0.01 mg/kg). Anesthesia was induced as in Part A. Onset times for the 4-min group were significantly faster than the 2- or 6-min groups. In Part C, the intubating dose was varied (0.07, 0.1, or 0.15 mg/kg iv) after the optimal priming dose and optimal priming interval (4 min). Onset times for the 0.1 mg/kg and 0.15 mg/kg groups were significantly faster than the 0.07 mg/kg group.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacokinetics of edrophonium and neostigmine when antagonizing d-tubocurarine neuromuscular blockade in man.

The pharmacokinetics and effectiveness of edrophonium antagonism of d-tubocurarine neuromuscular blockade were compared with that of neostigmine in surgical patients anesthetized with halothane and nitrous oxide. After an intravenous (iv) injection of d-tubocurarine (0.3 mg/kg), the single twitch tension was allowed to return to five per cent of the control level. Edrophonium, 0.5 or 1.0 mg/kg (n = 12), or neostigmine, 0.07 mg/kg (n = 6), was then given iv in combination with atropine, 1.0 mg, as a 2-min controlled infusion. Train-of-four and single twitch tension were followed for 60 min in all patients. Twelve patients were monitored for 90 min, six patients for 120 min, four patients for 150 min, and two patients for 240 min. Blood was sampled intermittently for four hours and assayed for edrophonium or neostigmine using high-pressure liquid chromatography. Edrophonium was found to promptly antagonize the d-tubocurarine blockade. Twitch tension rapidly increased to a plateau (a rate of increase in twitch tension of less than 2 per cent of control per min) which was sustained in all cases. The mean time to plateau for edrophonium was 2.9 +/- 0.21 (+/-SE) min as compared to 6.1 +/- 0.75 min for neostigmine. Neuromuscular blockade did not reappear in any patient. The degree of antagonism of the neuromuscular blockade by neostigmine and edrophonium was not significantly different. Except for a longer distribution half-life, the pharmacokinetic variables for edrophonium did not differ significantly from those for neostigmine. The elimination half-lives of edrophonium and neostigmine were 110 +/- 34 min (mean +/- SD) and 77 +/- 47 min, respectively. The authors therefore conclude that edrophonium, 0.5-1.0 mg/kg, has pharmacokinetic variables comparable to neostigmine and produces prompt, sustained, and effective antagonism of d-tubocurarine neuromuscular blockade.

Effect of dibutyryl cyclic AMP on neuromuscular transmission in myasthenia gravis.

The effect of dibutyryl 3',5'-cyclic monophosphate (D-cAMP) on the neuromuscular transmission was studied in a patient with myasthenia gravis during anesthesia. D-cAMP caused a slight increase in single twitch tension, and an initial transient decrease in tension which resulted from the trains of 2 Hz stimuli disappeared after D-cAMP. The finding of the present study suggests that D-cAMP has an anti-fatigue effect in patients with myasthenia gravis.

Adverse interaction between steroid hormones and anticholinesterase drugs.

Hydrocortisone, despite its lack of effect when used alone in a rat nervemuscle preparation, abolished the increase in muscle single-twitch tension produced by the anticholinesterase drugs neostigmine and pyridostigmine. Once the steroid had abolished the effect of these drugs, equivalent doses of the cholinesterase inhibitors were less effective than they had been before steroid was given. The results of these experiments indicate that a corticosteroid hormone may have an adverse pharmacologic interaction with anticholinesterase drugs in a mammalian nerve-muscle preparation. This significant adverse interaction might be the reason some patients with myasthenia gravis do not respond as well with corticosteroid plus anticholinesterase as with corticosteroid alone.