Denervation stage differentially influences resistance to neuromuscular blockers in rat gastrocnemius

Yang, Bin; Jiang, Jihong; Zhou, Yachun; Zhang, Ying; Li, Shitong

doi:10.1016/j.jss.2012.11.002

Cited by 13 publications

(9 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is possibly due to the relative contribution of the isolated effects of systemic inflammation and sepsis, immobilization and denervation to the resulting overall AChR expression in each model. For instance, denervation is expected to increase expression of AChR of immature isoforms (788). Immobilization, as a contributing correlate to ICUAW (214), either resulted in increased (214,461) or unaltered receptor expression (337) in the immobilized limb.…”

Section: B Neuromuscular Transmission In Sepsis and Systemic Inflammmentioning

confidence: 99%

The Sick and the Weak: Neuropathies/Myopathies in the Critically Ill

Friedrich

Reid

Berghe

et al. 2015

Physiological Reviews

293

329

View full text Add to dashboard Cite

Critical illness polyneuropathies (CIP) and myopathies (CIM) are common complications of critical illness. Several weakness syndromes are summarized under the term intensive care unit-acquired weakness (ICUAW). We propose a classification of different ICUAW forms (CIM, CIP, sepsis-induced, steroid-denervation myopathy) and pathophysiological mechanisms from clinical and animal model data. Triggers include sepsis, mechanical ventilation, muscle unloading, steroid treatment, or denervation. Some ICUAW forms require stringent diagnostic features; CIM is marked by membrane hypoexcitability, severe atrophy, preferential myosin loss, ultrastructural alterations, and inadequate autophagy activation while myopathies in pure sepsis do not reproduce marked myosin loss. Reduced membrane excitability results from depolarization and ion channel dysfunction. Mitochondrial dysfunction contributes to energy-dependent processes. Ubiquitin proteasome and calpain activation trigger muscle proteolysis and atrophy while protein synthesis is impaired. Myosin loss is more pronounced than actin loss in CIM. Protein quality control is altered by inadequate autophagy. Ca 2ϩ dysregulation is present through altered Ca 2ϩ homeostasis. We highlight clinical hallmarks, trigger factors, and potential mechanisms from human studies and animal models that allow separation of risk factors that may trigger distinct mechanisms contributing to weakness. During critical illness, altered inflammatory (cytokines) and metabolic pathways deteriorate muscle function. ICUAW prevention/treatment is limited, e.g., tight glycemic control, delaying nutrition, and early mobilization. Future challenges include identification of primary/secondary events during the time course of critical illness, the interplay between membrane excitability, bioenergetic failure and differential proteolysis, and finding new therapeutic targets by help of tailored animal models.

show abstract

Section: B Neuromuscular Transmission In Sepsis and Systemic Inflammmentioning

confidence: 99%

The Sick and the Weak: Neuropathies/Myopathies in the Critically Ill

Friedrich

Reid

Berghe

et al. 2015

Physiological Reviews

293

329

View full text Add to dashboard Cite

show abstract

“…As the absolute number of acetylcholine receptors increases, the given plasma concentration of the NMBA provides less neuromuscular suppression. 10,15,16 Alternatively, since our patient sustained a spinal cord injury, it is possible that upregulation of acetylcholine receptors could be part of the cause of the resistance to rocuronium and cisatracurium. Finally, given the presence of spinal Am J Health-Syst Pharm-Vol 72 Apr 15, 2015 shock, it is possible that dysregulation of the sympathetic innervation to the microvasculature may have impaired perfusion to muscle and therefore delivery of NMBAs.…”

Section: Discussionmentioning

confidence: 99%

“…The potential downregulation of the immature acetylcholine receptors required upregulation to occur again when the NMBA was restarted, resulting in a delay in tachyphylaxis development. 10,16,17 The etiology of resistance to NMBAs may be due to alterations in pharmacodynamics and pharmacokinetics. The exact mechanism of resistance for our patient could not be determined.…”

Section: Discussionmentioning

confidence: 99%

Resistance to rocuronium and cisatracurium in a patient with a spinal injury and acute respiratory distress syndrome

Riley

Yampolsky

Hakma³

et al. 2015

American Journal of Health-System Pharmacy

View full text Add to dashboard Cite

show abstract

“…However, the magnitude of resistance to NDMRs changed after skeletal muscle denervation [3]. The different strength of resistance to NDMRs resulted in the altered requirement for NDMRs at different times after denervation [4].…”

Section: Introductionmentioning

confidence: 99%

γ-Acetylcholine Receptor Mediating Dynamic Changes of Resistance to Rocuronium in the Denervated Skeletal Muscle

Wang

Chen

et al. 2018

Pharmacology

Self Cite

View full text Add to dashboard Cite

Background/Aims: Denervation resulted in resistance to non-depolarizing muscle relaxants (NDMRs), the magnitude of which changed after denervation in the skeletal muscle. The aim of this study was to investigate whether changed potencies of rocuronium were due to altered γ-acetylcholine receptor (γ-AChR) expression after skeletal muscle denervation. Methods: Innervated and denervated muscle cells were used in this study. Patch clamp and Western blotting techniques were separately applied to examine IC₅₀ values of rocuronium and γ-AChR protein expression at different times after denervation. Then, using the linear Pearson correlation analysis, the relationship between IC₅₀ values of rocuronium and γ-AChR expression was tested. Results: Compared with the innervated control, both IC₅₀ values of rocuronium and γ-AChR expression significantly increased at Day 4, 7, and 14 after denervation in the skeletal muscle. Furthermore, γ-AChR protein and IC₅₀ values of rocuronium exibited a significant positive correlation (r = 0.7678, p < 0.0001). Conclusion: These above results indicated that dynamic changes of resistance to NDMRs may be due to altered γ-AChR expression after skeletal muscle denervation.

show abstract

Denervation stage differentially influences resistance to neuromuscular blockers in rat gastrocnemius

Cited by 13 publications

References 18 publications

The Sick and the Weak: Neuropathies/Myopathies in the Critically Ill

The Sick and the Weak: Neuropathies/Myopathies in the Critically Ill

Resistance to rocuronium and cisatracurium in a patient with a spinal injury and acute respiratory distress syndrome

γ-Acetylcholine Receptor Mediating Dynamic Changes of Resistance to Rocuronium in the Denervated Skeletal Muscle

Contact Info

Product

Resources

About