Resistance to d-Tubocurarine of the Rat Diaphragm as Compared to a Limb Muscle

Nguyen-Huu, Tu; Molgó, Jordi; Servent, Denis; Duvaldestin, P.

doi:10.1097/aln.0b013e31819faeaa

Cited by 25 publications

(9 citation statements)

References 25 publications

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“…values, P B 0.05 than in the Tibialis anterior muscle, where pronounced tetanic fade was observed at frequencies above 50 Hz(Mouisel et al 2006). Superior adaptation of the diaphragm is consistent with its critical role in the survival of the animal(Nguyen-Huu et al 2009). Representative MEPPs recorded from AChE ?/?…”

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confidence: 75%

Role of Acetylcholinesterase on the Structure and Function of Cholinergic Synapses: Insights Gained from Studies on Knockout Mice

Adler¹,

Sweeney²,

Hamilton³

et al. 2011

Cell Mol Neurobiol

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Electrophysiological and ultrastructural studies were performed on phrenic nerve-hemidiaphragm preparations isolated from wild-type and acetylcholinesterase (AChE) knockout (KO) mice to determine the compensatory mechanisms manifested by the neuromuscular junction to excess acetylcholine (ACh). The diaphragm was selected since it is the primary muscle of respiration, and it must adapt to allow for survival of the organism in the absence of AChE. Nerve-elicited muscle contractions, miniature endplate potentials (MEPPs) and evoked endplate potentials (EPPs) were recorded by conventional electrophysiological techniques from phrenic nerve-hemidiaphragm preparations isolated from 1.5- to 2-month-old wild-type (AChE(+/+)) or AChE KO (AChE(-/-)) mice. These recordings were chosen to provide a comprehensive assessment of functional alterations of the diaphragm muscle resulting from the absence of AChE. Tension measurements from AChE(-/-) mice revealed that the amplitude of twitch tensions was potentiated, but tetanic tensions underwent a use-dependent decline at frequencies below 70 Hz and above 100 Hz. MEPPs recorded from hemidiaphragms of AChE(-/-) mice showed a reduction in frequency and a prolongation in decay (37%) but no change in amplitude compared to values observed in age-matched wild-type littermates. In contrast, MEPPs recorded from hemidiaphragms of wild-type mice that were exposed for 30 min to the selective AChE inhibitor 5-bis(4-allyldimethyl-ammoniumphenyl)pentane-3-one (BW284C51) exhibited a pronounced increase in amplitude (42%) and a more marked prolongation in decay (76%). The difference between MEPP amplitudes and decays in AChE(-/-) hemidiaphragms and in wild-type hemidiaphragms treated with BW284C51 represents effective adaptation by the former to a high ACh environment. Electron microscopic examination revealed that diaphragm muscles of AChE(-/-) mice had smaller nerve terminals and diminished pre- and post-synaptic surface contacts relative to neuromuscular junctions of AChE(+/+) mice. The morphological changes are suggested to account, in part, for the ability of muscle from AChE(-/-) mice to function in the complete absence of AChE.

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confidence: 75%

Role of Acetylcholinesterase on the Structure and Function of Cholinergic Synapses: Insights Gained from Studies on Knockout Mice

Adler¹,

Sweeney²,

Hamilton³

et al. 2011

Cell Mol Neurobiol

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“…Although a TOF ratio > 0.9 in the adductor pollicis rules out residual curarization, the diaphragm is often not evaluated in the operating room. The diaphragm is the most highly resistant muscle to NMBAs, as well as the first to recover [ 14 ], but the occurrence of its dysfunction has been implicated in postoperative respiratory failure, especially when mechanical ventilation is prolonged [ 15 , 16 ]. Therefore, studying diaphragmatic function in a perioperative context is extremely important.…”

Section: Introductionmentioning

confidence: 99%

Recovery of muscle function after deep neuromuscular block by means of diaphragm ultrasonography and adductor of pollicis acceleromyography with comparison of neostigmine vs. sugammadex as reversal drugs: study protocol for a randomized controlled trial

Cappellini

Picciafuochi

Ostento

et al. 2018

Trials

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BackgroundThe extensive use of neuromuscular blocking agents (NMBAs) during surgical procedures still leads to potential residual paralyzing effects in the postoperative period. Indeed, neuromuscular monitoring in an intra-operative setting is strongly advocated. Acetylcholinesterase inhibitors can reverse muscle block, but their short half-life may lead to residual curarization in the ward, especially when intermediate or long-acting NMBAs have been administered. Sugammadex is the first selective reversal drug for steroidal NMBAs; it has been shown to give full and rapid recovery of muscle strength, thus minimizing the occurrence of residual curarization. Acceleromyography of the adductor pollicis is the gold standard for detecting residual curarization, but it cannot be carried out on conscious patients. Ultrasonography of diaphragm thickness may reveal residual effects of NMBAs in conscious patients.Methods/designThis prospective, double-blind, single-center randomized controlled study will enroll patients (of American Society of Anesthesiologists physical status I–II, aged 18–80 years) who will be scheduled to undergo deep neuromuscular block with rocuronium for ear, nose, or throat surgery. The study’s primary objective will be to compare the effects of neostigmine and sugammadex on postoperative residual curarization using two different tools: diaphragm ultrasonography and acceleromyography of the adductor pollicis. Patients will be extubated when the train-of-four ratio is > 0.9. Diaphragm ultrasonography will be used to evaluate the thickening fraction, which is the difference between the end expiratory thickness and the end inspiratory thickness, normalized to the end expiratory thickness. Ultrasonography will be performed before the initiation of general anesthesia, before extubation, and 10 and 30 min after discharging patients from the operating room. The secondary objective will be to compare the incidence of postoperative complications due to residual neuromuscular block between patients who receive neostigmine and those who receive sugammadex.DiscussionPostoperative residual curarization is a topic of paramount importance, because its occurrence can cause complications and increase the length of stay in hospital and the related costs. Diaphragm ultrasound assessment may become a bedside integrative tool in the neuromuscular monitoring field to detect concealed residual curarization in surgical patients who have received paralyzing agents.Trial registrationEudraCT, 2013-004787-62. Registered on 18 June 2014, as “Evaluation of muscle function recovery after deep neuromuscular blockade by acceleromyography of the adductor pollicis or diaphragmatic echography: comparison between sugammadex and neostigmine.”ClinicalTrials.gov, NCT02698969. Registered on 15 February 2016, as “Recovery of Muscle Function After Deep Neuromuscular Block by Means of Diaphragm Ultrasonography and Adductor Pollicis Acceleromyography: Comparison of Neostigmine vs. Sugammadex as Reversal Drugs.”Electronic supplementary materialT...

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“…The SF relies on both the amount of presynaptic transmitter released per nerve impulse, being greater than that required to trigger an action potential in the muscle fiber, and on elaborate postsynaptic specializations to enhance the transmitter response [ 58 , 59 ]. It also relies on the diaphragm, possessing a higher density of nAChR and ACh quantal contents than peripheral muscles [ 23 ]. This means that the SF makes the diaphragm more capable of amplifying the responses to depolarization, promoting the transduction process that leads to contraction than EDL and SOL muscles.…”

Section: Resultsmentioning

confidence: 99%

“…The diaphragm is a muscle with distinctive physiological properties when compared with peripheral muscles; it is resistant to the blocking effects of competitive neuromuscular blocking agents due to the high concentration of quanta of ACh released after stimulation and greater number of occupied postsynaptic nicotinic receptors [ 23 ]; along with a low acetylcholinesterase activity at the synaptic cleft [ 24 ] and a major quantal content when compared, for example, with EDL [ 23 ]. Moreover, the diaphragm muscle comprises motor units varying in their mechanical and fatigue properties and which rely on the fiber type motor innervation control [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

Guanidine Affects Differentially the Twitch Response of Diaphragm, Extensor Digitorum Longus and Soleus Nerve-Muscle Preparations of Mice

2012

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Guanidine has been used with some success to treat myasthenia gravis and myasthenic syndrome because it increases acetylcholine release at nerve terminals through K+, Na+ and Ca2+ channels-involving mechanisms. Currently, guanidine derivatives have been proposed for treatment of several diseases. Studies aimed at providing new insights to the drug are relevant. Experimentally, guanidine (10 mM) induces on mouse phrenic nerve-diaphragm (PND) preparations neurotransmission facilitation followed by blockade and a greatest secondary facilitation after its removal from bath. Herein, we hypothesized that this peculiar triphasic response may differ in muscles with distinct twitch/metabolic characteristics. Morphological alterations and contractile response of PND, extensor digitorum longus (EDL) and soleus (SOL) preparations incubated with guanidine (10 mM) for 15, 30, 60 min were analyzed. Guanidine concentrations of 5 mM (for PND and EDL) and 1 mM (for EDL) were also tested. Guanidine triphasic effect was only observed on PND regardless the concentration. The morphological alterations in muscle tissue varied along time but did not impede the PND post-wash facilitation. Higher doses (20–25 mM) did not increase EDL or SOL neurotransmission. The data suggest a complex mechanism likely dependent on the metabolic/contractile muscle phenotype; muscle fiber types and density/type of ion channels, sarcoplasmic reticulum and mitochondria organization may have profound impact on the levels and isoform expression pattern of Ca2+ regulatory membrane proteins so reflecting regulation of calcium handling and contractile response in different types of muscle.

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Resistance to d-Tubocurarine of the Rat Diaphragm as Compared to a Limb Muscle

Abstract: The current study indicates that the resistance of the diaphragm to neuromuscular blocking agents can be explained by both a higher mean quantal content of endplate potentials and a higher number of nicotinic acetylcholine receptor binding sites than in the peripheral EDL muscle.

Cited by 25 publications

References 25 publications

Role of Acetylcholinesterase on the Structure and Function of Cholinergic Synapses: Insights Gained from Studies on Knockout Mice

Role of Acetylcholinesterase on the Structure and Function of Cholinergic Synapses: Insights Gained from Studies on Knockout Mice

Recovery of muscle function after deep neuromuscular block by means of diaphragm ultrasonography and adductor of pollicis acceleromyography with comparison of neostigmine vs. sugammadex as reversal drugs: study protocol for a randomized controlled trial

Guanidine Affects Differentially the Twitch Response of Diaphragm, Extensor Digitorum Longus and Soleus Nerve-Muscle Preparations of Mice

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