Ionic and Cellular Mechanisms Underlying the Development of Acquired Brugada Syndrome in Patients Treated with Antidepressants

Minoura, Yoshino; Diego, José M. Di; Barajas-Martínez, Héctor; Zygmunt, Andrew C.; Hu, Dan; Sicouri, Serge; Antzelevitch, Charles

doi:10.4020/jhrs.27.cp2_01

Cited by 5 publications

(10 citation statements)

References 28 publications

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“…) but also amitriptyline has a variety of adverse effects due to its anticholinergic and antihistaminergic properties (Stahl, ), and it can cause cardiac arrythmias (Minoura et al . ). Cardiac arrythmias may be particularly critical considering the involvement of cardiac muscle in DMD (Judge et al .…”

Section: Discussionmentioning

confidence: 97%

“…In conjunction with previous studies, this shows that glucocorticoids and amitriptyline both have the potential to reduce muscle inflammation and restore muscle function (Manzur et al 2008;Carre-Pierrat et al 2011). However, not only glucocorticoids (Manzur et al 2008) but also amitriptyline has a variety of adverse effects due to its anticholinergic and antihistaminergic properties (Stahl, 1998), and it can cause cardiac arrythmias (Minoura et al 2012). Cardiac arrythmias may be particularly critical considering the involvement of cardiac muscle in DMD (Judge et al 2011).…”

Section: Effect Of Amitriptyline On Muscle Inflammationmentioning

confidence: 99%

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Amitriptyline is efficacious in ameliorating muscle inflammation and depressive symptoms in the mdx mouse model of Duchenne muscular dystrophy

Manning

Kulbida

Rai

et al. 2014

Experimental Physiology

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New Findings r What is the central question of this study?Individuals suffering from Duchenne muscular dystrophy show progressive deterioration of muscle function associated with muscle inflammation and are susceptible to anxiety and depression. The central question in this study is whether the tricyclic antidepressant amitriptyline can alleviate symptoms of anxiety and depression, and at the same time has anti-inflammatory effects in mdx mice, which are a model of Duchenne muscular dystrophy. r What is the main finding and its importance?Amitriptyline reduced inflammation and cytokines in mdx skeletal muscle, and had anxiolytic and antidepressant effects in mdx mice. Moreover, amitriptyline elevated the level of serotonin but reduced the expression of the cytokine interleukin-6 in the amygdala of mdx mice.Mutations in the structural protein dystrophin underlie muscular dystrophies characterized by progressive deterioration of muscle function. Dystrophin-deficient mdx mice are considered a model for Duchenne muscular dystrophy (DMD). Individuals with DMD are also susceptible to mood disorders, such as depression and anxiety. Therefore, the study objectives were to investigate the effects of the tricyclic antidepressant amitriptyline on mood, learning, central cytokine expression and skeletal muscle inflammation in mdx mice. Amitriptyline-induced effects (10 mg kg −1 daily s.c. injections, 25 days) on the behaviour of mdx mice were investigated using the open field arena and tail suspension tests. The effects of chronic amitriptyline treatment on inflammatory markers were studied in the muscle and plasma of mdx mice, and mood-associated monoamine and cytokine concentrations were measured in the amygdala, hippocampus, prefrontal cortex, striatum, hypothalamus and midbrain. The mdx mice exhibited increased levels of anxiety and depressive-like behaviour compared with wild-type mice. Amitriptyline treatment had anxiolytic and antidepressant effects in mdx mice associated with elevations in serotonin levels in the amygdala and hippocampus. Inflammation in mdx skeletal muscle tissue was also reduced following amitriptyline treatment as indicated by decreased immune cell infiltration of muscle and lower levels of the pro-inflammatory cytokines tumour

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Section: Discussionmentioning

confidence: 97%

Section: Effect Of Amitriptyline On Muscle Inflammationmentioning

confidence: 99%

Amitriptyline is efficacious in ameliorating muscle inflammation and depressive symptoms in the mdx mouse model of Duchenne muscular dystrophy

Manning

Kulbida

Rai

et al. 2014

Experimental Physiology

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“…29,30 The agents that block peak sodium channel current (I Na ) generally block late I Na , which can contribute to the action potential duration and QT-interval shortening. This mechanism may underlie the effect of lamotrigine and valproic acid to exacerbate the action of rufinamide to shorten the QT interval.…”

Section: Discussionmentioning

confidence: 99%

Drug-induced QT-interval shortening following antiepileptic treatment with oral rufinamide

Schimpf¹,

Veltmann²,

Papavassiliu³

et al. 2012

Heart Rhythm

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BACKGROUND The arrhythmogenic potential of short QT intervals has recently been highlighted in patients with a short QT syndrome. Drug-induced QT-interval prolongation is a known risk factor for ventricular tachyarrhythmias. However, reports on drug-induced QT-interval shortening are rare and proarrhythmic effects remain unclear. OBJECTIVE Recently, rufinamide, a new antiepileptic drug for the add-on treatment of Lennox-Gastaut syndrome, was approved in the European Union and the United States. Initial trials showed drug-induced QT-interval shortening. The aim of our study was to evaluate the effects of rufinamide on QT intervals in patients with difficult-to-treat epilepsies. METHODS Nineteen consecutive patients with Lennox-Gastaut syndrome and other epilepsy syndromes were included (n = 12 men; mean age 41 ± 12 years). QRS, QT, and Tpeak-Tend intervals were analyzed before and during rufinamide treatment. RESULTS The mean QT interval shortened significantly following rufinamide administration (QT interval 349 ± 23 ms vs 327 ± 17 ms; corrected QT interval 402 ± 22 ms vs 382 ± 16 ms; P = .002). Tpeak-Tend intervals were 79 ± 17 ms before and 70 ± 20 ms on treatment (P = .07). The mean reduction of the corrected QT interval was 20 ± 18 ms. During follow-up (3.04 ± 1.09 years), no adverse events including symptomatic cardiac arrhythmias or sudden cardiac deaths were observed. CONCLUSION QTc-interval shortening following oral rufinamide administration in a small patient group was not associated with significant clinical adverse effects. These observations nothwithstanding, the ability of rufinamide to significantly shorten the QT interval portends a potential arrhythmogenic risk that may best be guarded against by periodic electrocardiographic recordings.

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“…The best drug currently available in the clinic capable of blocking I to is quinidine. Quinidine was first recommended as therapy for BrS by our group in 1999 based on experimental evidence acquired using the coronary‐perfused RV wedge model of BrS , . Clinical evidence for the effectiveness of quinidine has been reported in numerous studies and case reports .…”

Section: Approaches To Therapy Of Jwsmentioning

confidence: 99%

“…Isoproterenol has been shown to be effective in quieting electrical storms developing in patients with both BrS and ERS . All of these agents have been shown to correct the repolarization defects responsible for development of phase 2 reentry and VT/VF in experimental models of BrS and ERS …”

Section: Approaches To Therapy Of Jwsmentioning

confidence: 99%

J wave syndromes as a cause of malignant cardiac arrhythmias

Diego

Antzelevitch

2018

Pacing Clinical Electrophis

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The J wave syndromes, including the Brugada (BrS) and early repolarization (ERS) syndromes, are characterized by the manifestation of prominent J waves in the electrocardiogram appearing as an ST segment elevation and the development of life-threatening cardiac arrhythmias. BrS and ERS differ with respect to the magnitude and lead location of abnormal J waves and are thought to represent a continuous spectrum of phenotypic expression termed J wave syndromes. Despite over 25 years of intensive research, risk stratification and the approach to therapy of these two inherited cardiac arrhythmia syndromes are still rapidly evolving. Our objective in this review is to provide an integrated synopsis of the clinical characteristics, risk stratifiers, as well as the molecular, ionic, cellular, and genetic mechanisms underlying these two syndromes that have captured the interest and attention of the cardiology community over the past two decades.

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Ionic and Cellular Mechanisms Underlying the Development of Acquired Brugada Syndrome in Patients Treated with Antidepressants

Cited by 5 publications

References 28 publications

Amitriptyline is efficacious in ameliorating muscle inflammation and depressive symptoms in the mdx mouse model of Duchenne muscular dystrophy

Amitriptyline is efficacious in ameliorating muscle inflammation and depressive symptoms in the mdx mouse model of Duchenne muscular dystrophy

Drug-induced QT-interval shortening following antiepileptic treatment with oral rufinamide

J wave syndromes as a cause of malignant cardiac arrhythmias

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