Increases in heart rate and systolic blood pressure in anesthetized dogs affected with X‐linked muscular dystrophy after cisatracurium administration: a retrospective study

Staffieri, Francesco; Sleeper, Margaret M.; Larenza, M. Paula

doi:10.1111/j.1460-9592.2011.03579.x

Cited by 3 publications

(5 citation statements)

References 19 publications

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“…Jurado, Mosing, Kutter, Boretti, and Bettschart‐Wolfensberger () observed increases in heart rate and mean arterial blood pressure in a dog after a cis‐atracurium overdose. Staffieri, Sleeper, and Larenza () also observed increases in arterial blood pressure and heart rate in dogs affected by X‐link muscular dystrophy. In the present study, increases in HR and arterial blood pressure were seen 5 min after cis‐atracurium administration in the pig.…”

Section: Discussionmentioning

confidence: 85%

“…In the present study, increases in HR and arterial blood pressure were seen 5 min after cis‐atracurium administration in the pig. Cis‐atracurium is now known to have antagonistic effects on M2 muscarinic receptors (Sanches Bornia, Bando, Machinski, Pereira, & Alves‐Do‐Prado, ; Staffieri et al., ). These effects on M2 receptors could result in increases in heart rate and arterial blood pressure if high doses of cis‐atracurium are administered.…”

Section: Discussionmentioning

confidence: 99%

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Neuromuscular block monitoring after the administration of 1 mg/kg intravenous cis‐atracurium in the anaesthetized pig

Aguilar

Moll

García

et al. 2018

Vet Pharm & Therapeutics

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Neuromuscular blocking agents should be included as part of a balanced anaesthetic protocol to improve anaesthetic management, although doses are not always established for each species. Cis-atracurium is a benzylisoquinolinium neuromuscular blocking agent with an intermediate duration of action devoid of significant adverse effects previously used in pigs with a wide dosage range. Cis-atracurium was administered at 1 mg/kg bolus to sixteen pigs to establish its time profile and effects. The pigs were premedicated intramuscularly with 4 mg/kg azaperone, 8 mg/kg ketamine and 0.2 mg/kg morphine IM and maintained with isoflurane in oxygen. After cis-atracurium administration, neuromuscular monitoring via acceleromyography was started until the recovery of the 90% of the train of four ratio. Complete decrease in the train of four ratio was accomplished in eleven pigs. Onset of action was 70 s, with a recovery of the fourth twitch at 26 min and a recovery of a train of four ratio greater than 90% in 60 min. In conclusion, 1 mg/kg intravenous cis-atracurium in the pig allowed for a rapid onset of action and a complete recovery after 60 min although high variability in the time profile is seen.

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Section: Discussionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Neuromuscular block monitoring after the administration of 1 mg/kg intravenous cis‐atracurium in the anaesthetized pig

Aguilar

Moll

García

et al. 2018

Vet Pharm & Therapeutics

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“…Recent reports have revealed that DMD patients often show low systolic blood pressure [ 16 , 17 ], and DMD patients with heart failure are also more susceptible to angiotensin receptor/neprilysin inhibitor with recurrent hypotension until discontinuation of this medication [ 6 ], suggesting that DMD might play a critical role in regulating blood pressure. However, a previous dog study [ 18 ], which generated some controversy, reported significantly increased systolic blood pressure in anesthetized dogs affected with X-linked muscular dystrophy (GRDM) after the administration of cisatracurium, a non-depolarizing neuromuscular blocking drug [ 18 ]. In this study, we compared blood pressure between DMD mut and control mice, and found that DMD mut mice exhibited lower blood pressure compared to their wide-type controls ( Figure 2 ), which addressed the role of DMD in the regulation of blood pressure.…”

Section: Discussionmentioning

confidence: 99%

Identification of Novel Gene Regulatory Networks for Dystrophin Protein in Vascular Smooth Muscle Cells by Single-Nuclear Transcriptome Analysis

Shen

Kim

Tang

2023

Cells

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Duchenne muscular dystrophy is an X-linked recessive disease caused by mutations in dystrophin proteins that lead to heart failure and respiratory failure. Dystrophin (DMD) is not only expressed in cardiomyocytes and skeletal muscle cells, but also in vascular smooth muscle cells (VSMCs). Patients with DMD have been reported to have hypotension. Single nuclear RNA sequencing (snRNA-seq) is a state-of-the-art technology capable of identifying niche-specific gene programs of tissue-specific cell subpopulations. To determine whether DMD mutation alters blood pressure, we compared systolic, diastolic, and mean blood pressure levels in mdx mice (a mouse model of DMD carrying a nonsense mutation in DMD gene) and the wide-type control mice. We found that mdx mice showed significantly lower systolic, diastolic, and mean blood pressure than control mice. To understand how DMD mutation changes gene expression profiles from VSMCs, we analyzed an snRNA-seq dataset from the muscle nucleus of DMD mutant (DMDmut) mice and control (Ctrl) mice. Gene Ontology (GO) enrichment analysis revealed that the most significantly activated pathways in DMDmut-VSMCs are involved in ion channel function (potassium channel activity, cation channel complex, and cation channel activity). Notably, we discovered that the DMDmut-VSMCs showed significantly upregulated expression of KCNQ5 and RYR2, whereas the most suppressed pathways were transmembrane transporter activity (such as anion transmembrane transporter activity, inorganic anion transmembrane transporter activity, import into cell, and import across plasma membrane). Moreover, we analyzed metabolic pathways from the Kyoto Encyclopedia of Genes and Genomes (KEGG) using “scMetabolism” R package. DMDmut-VSMCs exhibited dysregulation of pyruvate metabolism and nuclear acid metabolism. In conclusion, via the application of snRNA-seq, we (for the first time) identify the potential molecular regulation by DMD in the upregulation of the expression of KCNQ5 genes in VSMCs, which helps us to understand the mechanism of hypotension in DMD patients. Our study potentially offers new possibilities for therapeutic interventions in systemic hypotension in DMD patients with pharmacological inhibition of KCNQ5.

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“…Cis‐atracurium has been shown to behave in vitro as a type 2 atrial muscarinic receptor (M2) antagonist (Staffieri et al. 2011).…”

mentioning

confidence: 99%

“…2011). The effects of M2 antagonism results in increased HR and APs in anaesthetized dogs affected by X‐linked muscular dystrophy (Staffieri et al. 2011).…”

mentioning

confidence: 99%

Cardiovascular effects of cis-atracurium overdose in a dog following misplacement of neuromuscular monitoring electrodes

Jurado

Mosing

Kutter

et al. 2012

Veterinary Anaesthesia and Analgesia

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Increases in heart rate and systolic blood pressure in anesthetized dogs affected with X‐linked muscular dystrophy after cisatracurium administration: a retrospective study

Abstract: In this report, increases in HR and SAP could be associated with the administration of cisatracurium in individuals affected with X-linked muscular dystrophy. These cardiovascular changes deserve further investigation.

Cited by 3 publications

References 19 publications

Neuromuscular block monitoring after the administration of 1 mg/kg intravenous cis‐atracurium in the anaesthetized pig

Neuromuscular block monitoring after the administration of 1 mg/kg intravenous cis‐atracurium in the anaesthetized pig

Identification of Novel Gene Regulatory Networks for Dystrophin Protein in Vascular Smooth Muscle Cells by Single-Nuclear Transcriptome Analysis

Cardiovascular effects of cis-atracurium overdose in a dog following misplacement of neuromuscular monitoring electrodes

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