Cell death of motoneurons in the chick embryo spinal cord. XI. Acetylcholine receptors and synaptogenesis in skeletal muscle following the reduction of motoneuron death by neuromuscular blockade

Development ◽  
1989 ◽  
Vol 107 (2) ◽  
pp. 331-341
Author(s):  
R.W. Oppenheim ◽  
S. Bursztajn ◽  
D. Prevette
Keyword(s):  
Skeletal Muscle ◽  
Cell Death ◽  
Neuromuscular Blockade ◽  
Normal Cell ◽  
Cell Loss ◽  
Complete Recovery ◽  
Neuromuscular Blocking ◽  
Motoneuron Survival ◽  
Neuromuscular Activity ◽  
Induced Changes

Treatment of chick embryos with neuromuscular blocking agents such as curare during periods of naturally occurring motoneuron death results in a striking reduction of this normal cell loss. Inactivity-induced changes in motoneuron survival were found to be associated with increased levels of AChRs and AChR-clusters in skeletal muscle and with increased focal sites of AChE that are innervated (‘synaptic sites’). Treatment of embryos with curare after the normal cell death period (E12-E15) resulted in no change in motoneuron survival. Although AChR-clusters and focal sites of AChE were increased in these embryos on E16, many of these sites were uninnervated. Treatment of embryos with nicotine or decamethonium (E6-E10) also reduced neuromuscular activity but did not alter motoneuron survival nor did such treatment alter AChRs. The different effects of curare vs nicotine and decamethoniam on motoneuron survival and AChRs may be related to the fact that the former is a competitive blocker whereas the latter two drugs are depolarizing blockers. Finally, treatment of embryos (E6-9) with doses of curare (1 mg daily) that allow for the almost complete recovery of neuromuscular activity a few days following treatment (by E16) resulted in the gradual loss of the excess motoneurons that were present on E10, and by E16 the number of remaining AChR clusters and focal sites of AChE were also decreased to levels comparable to control values. Inactivity-induced changes in AChRs or AChR-clusters may be an important factor in the reduced motoneuron death that accompanies neuromuscular blockade during critical stages of development. These receptor changes very likely reflect increased synaptogenesis in the muscles of paralyzed embryos which in turn may act to reduce motoneuron death by providing increased access to muscle-derived neurotrophic molecules.

The effect of a benzodiazepine, flurazepam, on the response of in vitro skeletal muscle preparations to muscle relaxants: are purines or their receptors involved?

1982 ◽  
Vol 60 (7) ◽  
pp. 877-884 ◽  
Author(s):  
John T. Hamilton ◽  
Peggy A. Stone
Keyword(s):  
Skeletal Muscle ◽  
Phrenic Nerve ◽  
Neuromuscular Blocking ◽  
Muscle Relaxants ◽  
Water Soluble ◽  
Neuromuscular Activity ◽  
Changing Trends ◽  
Low Concentrations ◽  
Partial Blockade

Changing trends in the use of anxiolytic agents and recent reassessment of their neuropharmacological activity has prompted this evaluation of the peripheral neuromuscular activity of the benzodiazepine, flurazepam. In previous reports we have documented peripheral neuromuscular activity of chlordiazepoxide and diazepam on the rat phrenic nerve diaphragm preparation. The water soluble benzodiazepine, flurazepam, has been studied on the rat phrenic nerve diaphragm and frog rectus abdominis in vitro. On the former preparation flurazepam enhanced and then blocked the response to indirect electrical stimulation (0.2 Hz) and readily blocked posttetanic potentiation and prevented the preparation from sustaining a tetanic contracture (30 Hz). On the later preparation, flurazepam blocked in a noncompetitive manner the response of the frog muscle to applied cholinergic agonists. Studies on the rat preparation with the neuromuscular blocking drug succinylcholine have shown an unexpected protection against blockade in preparations pretreated with low concentrations of flurazepam. This was not observed when flurazepam was given prior to d-tubocurarinc. The application of adenosine to rat diaphragms during steady-state partial blockade caused by flurazepam or d-tubocurarine showed an inhibiting action of adenosine which was reversed by theophylline. Pretreatment of rat preparations with dipyridamole significantly enhanced the blocking action of standard concentrations of succinylcholine.These results, along with those in the literature, encourage a reassessment of the action of purines and benzodiazepines on skeletal muscle and encourage a consideration of a possible involvement of purinergic neuromodulation of transmission which is unmasked when the safety factor for transmission is altered by muscle relaxants. The possible clinical significance of protection against succinylcholine by benzodiazepines is noted.

Neuromuscular blockade increases motoneurone survival during normal cell death in the chick embryo

Nature ◽  
1978 ◽  
Vol 271 (5643) ◽  
pp. 364-366 ◽  
Author(s):  
R. H. PITTMAN ◽  
R. W. OPPENHEIM
Keyword(s):  
Cell Death ◽  
Chick Embryo ◽  
Neuromuscular Blockade ◽  
Normal Cell

Forearm blood flow responses to handgripping after local neuromuscular blockade

1998 ◽  
Vol 84 (2) ◽  
pp. 754-758 ◽  
Author(s):  
Christopher K. Dyke ◽  
Niki M. Dietz ◽  
Robert L. Lennon ◽  
David O. Warner ◽  
Michael J. Joyner
Keyword(s):  
Skeletal Muscle ◽  
Heart Rate ◽  
Blood Flow ◽  
Neuromuscular Blockade ◽  
Drug Administration ◽  
Forearm Blood Flow ◽  
Maximum Voluntary Contraction ◽  
Voluntary Contraction ◽  
Neuromuscular Blocking ◽  
Motor Nerves

Dyke, Christopher K., Niki M. Dietz, Robert L. Lennon, David O. Warner, and Michael J. Joyner. Forearm blood flow responses to handgripping after local neuromuscular blockade. J. Appl. Physiol. 84(2): 754–758, 1998.—To test the hypothesis that acetylcholine “spillover” from motor nerves contributes significantly to skeletal muscle vasodilation during exercise, we measured the forearm blood flow responses during attempted handgripping after local paralysis of the forearm with the neuromuscular-blocking drug pipecuronium. This compound blocks postsynaptic nicotinic receptors but has no impact on acetylcholine release from motor nerves. The drug was administered selectively to one forearm by using regional intravenous drug administration techniques in five subjects. Pipecuronium reduced maximum forearm grip strength from 40.0 ± 3.2 kg before treatment to 0.0 kg after treatment. By contrast, drug administration had no effect on maximum voluntary contraction in the untreated forearm (41.3 ± 3.3 vs. 41.4 ± 2.7 kg). During 2 min of attempted maximal contraction of the paralyzed forearm, the forearm blood flow increased from only 3.4 ± 0.8 to 4.8 ± 1.2 ml ⋅ 100 ml−1 ⋅ min−1( P < 0.05). Heart rate increased from 63 ± 3 to 73 ± 8 beats/min ( P > 0.05) during attempted contraction, and only three of five subjects showed obvious increases in heart rate. Mean arterial pressure increased significantly ( P < 0.05) from 102 ± 6 to 109 ± 9 mmHg during attempted contractions. When these increases in flow are considered in the context of the marked (10-fold or greater) increases in flow seen in contracting forearm skeletal muscle, it appears that acetylcholine spillover from motor nerves has, at most, a minimal impact on the hyperemic responses to contraction in humans.

scholarly journals Effect of intravenous infusion of rocuronium on emergence from propofol anesthesia in rats

2020 ◽  
Author(s):  
Kaoru Suzuki ◽  
Hiroshi Sunaga ◽  
Kentaro Yamakawa ◽  
Yoshifumi Suga ◽  
Ichiro Kondo ◽  
...  
Keyword(s):  
Continuous Infusion ◽  
Neuromuscular Blockade ◽  
Normal Saline ◽  
Case Reports ◽  
Complete Recovery ◽  
Cerebrovascular Diseases ◽  
Neuromuscular Blocking ◽  
Neuromuscular Blocking Agents ◽  
Sprague Dawley ◽  
Blocking Agents

Abstract Background: Central nervous system effects of neuromuscular blocking agents have been indicated in some case reports. We investigated whether intravenous (IV) infusion of rocuronium affects emergence from propofol anesthesia in rats. Methods: We used Sprague Dawley rats. Propofol infusion was initiated with a bolus of 15 mg/kg and continued at a rate of 40 mg/kg/h. For the rocuronium group (n = 18), rocuronium was administered as an initial IV bolus of 5 mg/kg followed by continuous infusion at a rate of 250, 500, or 1000 μg/kg/min along with propofol infusion. Infusion was continued for 60 min, and sugammadex (32 mg/kg) was injected at the end of infusion. In a separate group of rats (n = 12), normal saline was administered along with propofol infusion. After continuous infusion for 60 min, normal saline or sugammadex (32 mg/kg) was injected. The time to emergence from propofol anesthesia was evaluated. To ascertain possible factors affecting emergence, the neuromuscular blocking, circulatory, and respiratory properties of IV rocuronium infusion at 1000 μg/kg/min were assessed (n = 18). Results: The time to emergence from propofol anesthesia was 239 ± 94 s after simultaneous infusion of normal saline without rocuronium and was 346 ± 78, 518 ± 134, and 638 ± 219 s after IV infusion of rocuronium at 250, 500, and 1000 μg/kg/min, respectively. The simultaneous IV infusion of rocuronium dose-dependently increased the time to emergence (ρ = 0.624; p = 0.006). Sugammadex alone did not delay emergence (280 ± 60 s; p = 0.39). Neuromuscular blockade induced by rocuronium at 1000 μg/kg/min was completely antagonized at 99 ± 21 s by sugammadex (32 mg/kg). Mean arterial pressure, heart rate, partial pressures of oxygen and carbon dioxide, and pH were not affected by rocuronium infusion. Conclusions: Our results show that IV infusion of rocuronium delays the emergence from propofol anesthesia in rats, despite the complete recovery from neuromuscular blockade by sugammadex. The use of neuromuscular blocking agents in neonates or patients with cerebrovascular diseases, whose blood-brain barrier might be immature or disrupted, should be carefully considered.

scholarly journals Recovery of early postoperative muscle strength after deep neuromuscular block by means of ultrasonography with comparison of neostigmine versus sugammadex as reversal drugs: study protocol for a randomised controlled trial

BMJ Open ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. e043935
Author(s):  
Xuan Wang ◽  
Yingyuan Li ◽  
Chanyan Huang ◽  
Wei Xiong ◽  
Qin Zhou ◽  
...  
Keyword(s):  
Randomised Controlled Trial ◽  
Muscle Strength ◽  
Neuromuscular Blockade ◽  
Postoperative Period ◽  
Controlled Trial ◽  
Complete Recovery ◽  
Early Postoperative Period ◽  
Time Points ◽  
Muscle Groups ◽  
Randomised Controlled

IntroductionDespite the use of quantitative neuromuscular monitoring together with the administration of reversal drugs (neostigmine or sugammadex), the incidence of residual neuromuscular blockade defined as a train-of-four ratio (TOFr) <0.9 remains high. Even TOFr >0.9 cannot ensure adequate recovery of neuromuscular function when T1 height is not recovered completely. Thus, a mathematical correction of TOFr needs to be applied because the return of a normal TOFr can precede the return of a normal T1 twitch height. On the other hand, different muscles have different sensitivities to neuromuscular blockade agents; thus, complete recovery of one specific muscle group does not represent complete recovery of all other muscles. Therefore, our study aims to assess the muscle strength recovery of respiratory-related muscle groups by ultrasound and evaluate global strength using handgrip dynamometry in the early postoperative period when TOFr=0.9 and corrected TOFr (cTOFr)=0.9 with comparison of neostigmine versus sugammadex as reversal drugs.Methods and analysisThis study will be a prospective, single-blinded, randomised controlled trial involving 60 patients with American Society of Anesthesiologists physical status I–II and aged between 18 and 65 years, who will undergo microlaryngeal surgery. We will assess geniohyoid muscle, parasternal intercostal muscle, diaphragm, abdominal wall muscle and handgrip strength at four time points: before anaesthesia, TOFr=0.9, cTOFr=0.9 and 30 min after admission to the post anaesthesia care unit. Our primary objective will be to compare the effects of neostigmine and sugammadex on the recovery of muscle strength of different muscle groups in the early postoperative period when TOFr=0.9 and cTOFr=0.9. The secondary objective will be to observe the difference of muscle strength between the time points of TOFr=0.9 and cTOFr=0.9 to find out the clinical significance of cTOFr >0.9.Ethics and disseminationThe protocol was reviewed and approved by the Ethics Committee of The First Affiliated Hospital, Sun Yat-sen University. The findings will be disseminated to the public through peer-reviewed scientific journals.Trial registration numberChiCTR2000033832.

scholarly journals Comparison of Train of Four Measurements with Kinemyography NMT DATEX and Accelerography TOFscan

2021 ◽  
Vol 9 (2) ◽  
pp. 21
Author(s):  
Cyrus Motamed ◽  
Migena Demiri ◽  
Nora Colegrave
Keyword(s):  
Neuromuscular Blockade ◽  
Lower Limit ◽  
Elective Surgery ◽  
Orotracheal Intubation ◽  
Neuromuscular Blocking ◽  
Physical Status Classification ◽  
Train Of Four ◽  
Surgery First ◽  
American Society ◽  
American Society Of Anesthesiologists

Introduction: This study was designed to compare the Datex neuromuscular transmission (NMT) kinemyography (NMTK) device with the TOFscan (TS) accelerometer during the onset and recovery of neuromuscular blockade. Patients and methods: This prospective study included adult patients who were scheduled to undergo elective surgery with general anesthesia and orotracheal intubation. The TS accelerometer was randomly placed at the adductor pollicis on one hand, and the NMTK was placed on the opposite arm. Anesthesia was initiated with remifentanil target-controlled infusion (TCI) and 2.0–3.0 mg/kg of propofol. Thereafter, 0.5 mg/kg of atracurium or 0.6 mg/kg of rocuronium was injected. If needed, additional neuromuscular blocking agents were administered to facilitate surgery. First, we recorded the train of four (TOF) response at the onset of neuromuscular blockade to reach a TOF count of 0. Second, we recorded the TOF response at the recovery of neuromuscular blockade to obtain a T4/T1 90% by both TS and NMTK. Results: There were 32 patients, aged 38–83 years, with the American Society of Anesthesiologists (ASA) Physical Status Classification I–III included and analyzed. Surgery was abdominal, gynecologic, or head and neck. The Bland and Altman analysis for obtaining zero responses during the onset showed a bias (mean) of 2.7 s (delay) of TS in comparison to NMTK, with an upper/lower limit of agreement of [104; −109 s] and a bias of 36 s of TS in comparison to NMTK, with an upper/lower limit of agreement of [−21.8, −23.1 min] during recovery (T4/T1 > 90%). Conclusions: Under the conditions of the present study, the two devices are not interchangeable. Clinical decisions for deep neuromuscular blockade should be made cautiously, as both devices appear less accurate with significant variability.

scholarly journals Neurotoxic Effect of Flavonol Myricetin in the Presence of Excess Copper

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 845
Author(s):  
Anja Sadžak ◽  
Ignacija Vlašić ◽  
Zoran Kiralj ◽  
Marijana Batarelo ◽  
Nada Oršolić ◽  
...  
Keyword(s):  
Cell Death ◽  
Intracellular Signaling ◽  
Chromatin Condensation ◽  
Membrane Integrity ◽  
Toxic Effects ◽  
Trypan Blue Exclusion ◽  
Atp Production ◽  
Mtt Method ◽  
Biophysical Approach ◽  
Induced Changes

Oxidative stress (OS) induced by the disturbed homeostasis of metal ions is one of the pivotal factors contributing to neurodegeneration. The aim of the present study was to investigate the effects of flavonoid myricetin on copper-induced toxicity in neuroblastoma SH-SY5Y cells. As determined by the MTT method, trypan blue exclusion assay and measurement of ATP production, myricetin heightened the toxic effects of copper and exacerbated cell death. It also increased copper-induced generation of reactive oxygen species, indicating the prooxidative nature of its action. Furthermore, myricetin provoked chromatin condensation and loss of membrane integrity without caspase-3 activation, suggesting the activation of both caspase-independent programmed cell death and necrosis. At the protein level, myricetin-induced upregulation of PARP-1 and decreased expression of Bcl-2, whereas copper-induced changes in the expression of p53, p73, Bax and NME1 were not further affected by myricetin. Inhibitors of ERK1/2 and JNK kinases, protein kinase A and L-type calcium channels exacerbated the toxic effects of myricetin, indicating the involvement of intracellular signaling pathways in cell death. We also employed atomic force microscopy (AFM) to evaluate the morphological and mechanical properties of SH-SY5Y cells at the nanoscale. Consistent with the cellular and molecular methods, this biophysical approach also revealed a myricetin-induced increase in cell surface roughness and reduced elasticity. Taken together, we demonstrated the adverse effects of myricetin, pointing out that caution is required when considering powerful antioxidants for adjuvant therapy in copper-related neurodegeneration.

scholarly journals Preclinical Pharmacology in the Rhesus Monkey of CW 1759-50, a New Ultra-short Acting Nondepolarizing Neuromuscular Blocking Agent, Degraded and Antagonized by L-Cysteine

2018 ◽  
Vol 129 (5) ◽  
pp. 970-988 ◽  
Author(s):  
John J. Savarese ◽  
Hiroshi Sunaga ◽  
Jeff D. McGilvra ◽  
Matthew R. Belmont ◽  
Matthew T. Murrell ◽  
...  
Keyword(s):  
Heart Rate ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Neuromuscular Blockade ◽  
Blocking Agent ◽  
Neuromuscular Blocking ◽  
Neuromuscular Blocking Agent ◽  
Duration Of Action ◽  
Short Acting ◽  
Circulatory Effects

Abstract Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Structure–activity studies were performed to identify a new neuromuscular blocking agent retaining the ultra-short acting characteristics of gantacurium, including degradation and reversal by l-cysteine, but lacking its histaminoid properties in man. CW 1759-50 has emerged from this program. Methods Adduction of CW 1759-50 with l-cysteine was studied by high-performance liquid chromatography and mass spectrometry. Institutional Animal Care and Use Committee–approved comparisons of CW 1759-50 to gantacurium were performed in rhesus monkeys. ED95 for neuromuscular blockade was established. Spontaneous recovery was compared to reversal by l-cysteine in paired studies of boluses or infusions. In addition, changes in mean arterial pressure and heart rate after very large doses of 15 to 60 × ED95 were compared. Results The half-time of adduction of l-cysteine to CW 1759-50 in vitro was 2.3 min. The ED95 of CW 1759-50 was 0.069 ± 0.02 mg/kg; ED95 of gantacurium was 0.081 ± 0.05 mg/kg (P = 0.006). Duration of action (recovery to 95% twitch height after 98 to 99% blockade) was as follows: CW 1759-50, 8.2 ± 1.5 min; and gantacurium, 7.4 ± 1.9 min; (n = 8 and 9, P = 0.355). Administration of l-cysteine (30 mg/kg) shortened recovery (i.e., induced reversal) from CW 1759-50 after boluses or infusions (P always less than 0.0001). Recovery intervals (5 to 95% twitch) ranged from 6.1 to 6.7 min (and did not differ significantly) after boluses of 0.10 to 0.50 mg/kg, as well as control infusions (P = 0.426 by analysis of variance). Dose ratios comparing changes of 30% in mean arterial pressure or heart rate to ED95 for neuromuscular blockade (ED 30% Δ [mean arterial pressure or heart rate]/ED95) were higher for CW 1759-50 than for gantacurium. Conclusions CW 1759-50, similar to gantacurium, is an ultra-short acting neuromuscular blocking agent, antagonized by l-cysteine, in the monkey. The circulatory effects, however, are much reduced in comparison with gantacurium, suggesting a trial in humans.

The Adaptive Potential of Skeletal Muscle Fibers

2002 ◽  
Vol 27 (4) ◽  
pp. 423-448 ◽  
Author(s):  
Dirk Pette
Keyword(s):  
Skeletal Muscle ◽  
Fiber Type ◽  
Muscle Fibers ◽  
Protein Isoforms ◽  
Mammalian Skeletal Muscle ◽  
Adaptive Potential ◽  
Hybrid Fibers ◽  
Neuromuscular Activity ◽  
Skeletal Muscle Fibers ◽  
Initial Location

Mammalian skeletal muscle fibers display a great adaptive potential. This potential results from the ability of muscle fibers to adjust their molecular, functional, and metabolic properties in response to altered functional demands, such as changes in neuromuscular activity or mechanical loading. Adaptive changes in the expression of myofibrillar and other protein isoforms result in fiber type transitions. These transitions occur in a sequential order and encompass a spectrum of pure and hybrid fibers. Depending on the quality, intensity, and duration of the alterations in functional demand, muscle fibers may undergo functional transitions in the direction of slow or fast, as well as metabolic transitions in the direction of aerobic-oxidative or glycotytic. The maximum range of possible transitions in either direction depends on the fiber phenotype and is determined by its initial location in the fiber spectrum. Key words: Ca-sequestering proteins, energy metabolism, fiber type transition, myofibrillar protein isofonns, myosin, neuromuscular activity

A group of genes required for maintenance of the amnioserosa tissue in Drosophila

Development ◽  
1996 ◽  
Vol 122 (5) ◽  
pp. 1343-1352 ◽  
Author(s):  
L.H. Frank ◽  
C. Rushlow
Keyword(s):  
Cell Death ◽  
Cell Loss ◽  
Dorsal Side ◽  
Drosophila Embryo ◽  
Epithelial Tissue ◽  
Dorsoventral Patterning ◽  
Wild Type ◽  
Germ Band ◽  
Initial Development

The amnioserosa is an extraembryonic, epithelial tissue that covers the dorsal side of the Drosophila embryo. The initial development of the amnioserosa is controlled by the dorsoventral patterning genes. Here we show that a group of genes, which we refer to as the U-shaped-group (ush-group), is required for maintenance of the amnioserosa tissue once it has differentiated. Using several molecular markers, we examined amnioserosa development in the ush-group mutants: u-shaped (ush), hindsight (hnt), serpent (srp) and tail-up (tup). Our results show that the amnioserosa in these mutants is specified correctly and begins to differentiate as in wild type. However, following germ-band extension, there is a premature loss of the amnioserosa. We demonstrate that this cell loss is a consequence of programmed cell death (apoptosis) in ush, hnt and srp, but not in tup. We discuss the role of the ush-group genes in maintaining the amnioserosa's viability. We also discuss a possible role for the amnioserosa in germ-band retraction in light of these mutants' unretracted phenotype.

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