Physiology: Beating stroke

Savage, Neil

doi:10.1038/493s12a

Cited by 5 publications

(6 citation statements)

References 8 publications

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“…Recent advances demonstrate the importance of the cardiac neural network in the pathophysiology of atrial fibrillation (AF). This is the most common sustained human arrhythmia, with a rising incidence of up to 10% in octogenarians, and leads to significant morbidity and mortality 2 3 . Cardiac neurons are inevitably obliterated during catheter ablation 4 , which is the therapy of choice for most patients suffering from symptomatic AF.…”

mentioning

confidence: 99%

Disruption of cardiac cholinergic neurons enhances susceptibility to ventricular arrhythmias

et al. 2017

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The parasympathetic nervous system plays an important role in the pathophysiology of atrial fibrillation. Catheter ablation, a minimally invasive procedure deactivating abnormal firing cardiac tissue, is increasingly becoming the therapy of choice for atrial fibrillation. This is inevitably associated with the obliteration of cardiac cholinergic neurons. However, the impact on ventricular electrophysiology is unclear. Here we show that cardiac cholinergic neurons modulate ventricular electrophysiology. Mechanical disruption or pharmacological blockade of parasympathetic innervation shortens ventricular refractory periods, increases the incidence of ventricular arrhythmia and decreases ventricular cAMP levels in murine hearts. Immunohistochemistry confirmed ventricular cholinergic innervation, revealing parasympathetic fibres running from the atria to the ventricles parallel to sympathetic fibres. In humans, catheter ablation of atrial fibrillation, which is accompanied by accidental parasympathetic and concomitant sympathetic denervation, raises the burden of premature ventricular complexes. In summary, our results demonstrate an influence of cardiac cholinergic neurons on the regulation of ventricular function and arrhythmogenesis.

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confidence: 99%

Disruption of cardiac cholinergic neurons enhances susceptibility to ventricular arrhythmias

et al. 2017

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“…Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, and its incidence is steadily on the rise (62). Currently, the lifetime risk of AF is 1:4 for men and women, and by the year 2050, over 12 million Americans will be affected (62,63).…”

Section: Atrial Fibrillationmentioning

confidence: 99%

“…Currently, the lifetime risk of AF is 1:4 for men and women, and by the year 2050, over 12 million Americans will be affected (62,63). AF remains an independent risk factor for the development of stroke, thromboembolism, heart failure, and impaired quality of life.…”

Section: Atrial Fibrillationmentioning

confidence: 99%

Proarrhythmic and Torsadogenic Effects of Potassium Channel Blockers in Patients

McCauley

Vallabhajosyula

Darbar

2016

Cardiac Electrophysiology Clinics

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Summary The most common arrhythmia requiring drug therapy is atrial fibrillation, which affects 2–5 million Americans and continues to be a major cause of morbidity and increased mortality. Despite recent advances in catheter-based and surgical therapies, antiarrhythmic drugs continue to be the mainstay of therapy for most patients with symptomatic AF. However, many antiarrhythmics block the rapid component of the cardiac delayed rectifier potassium current (IKr) as a major mechanism of action, and marked QT prolongation and pause-dependent polymorphic ventricular tachycardia (torsades de pointes) are major class toxicities. Although this arrhythmia is usually seen in patients with one of the congenital long QT syndromes, torsades de pointes has also been observed with certain antibiotics, antipsychotics, antihistamines and chemotherapeutic agents and is a leading cause of post-market drug withdrawal and relabeling. Clinical risk factors associated with drug-induced long QT syndrome include female gender, bradycardia, electrolyte disturbances, recent conversion from atrial fibrillation to sinus rhythm, variations in drug distribution and sub-clinical long QT syndrome. A unifying concept of reduced repolarization reserve has been proposed to explain the variable risk of torsades de pointes. In this monograph, we provide a historical perspective on drug-induced long QT syndrome, briefly discuss the underlying mechanisms, and detail recent advances in torsadogenic risk factors and the complex interplay between individual patient-related clinical risk characteristics and the development of torsades de pointes with potassium-channel blocking drugs.

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“…While AF is the cause of 25% of embolic strokes, the mechanism is still not truly understood. It is thought that clots form inside the heart, due to the rapid irregular beating, whereby these clots travel into arteries and block the blood supply to the brain [22]. The classical treatment for AF has been a vitamin K antagonist, which is an anti-coagulant that decreases the risk of stroke by 60%.…”

Section: Coagulation Cascade: Thrombotic Diseasesmentioning

confidence: 99%

Small molecule inhibitors in the treatment of cerebral ischemia

Flores

Zhang

Klebe

et al. 2014

Expert Opinion on Pharmacotherapy

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Many studies demonstrated that pre- or post-treatment with certain SMIs significantly ameliorated adverse effects from stroke. Although some of these promising SMIs moved on to clinical trials, they generally failed, possibly due to the poor translation of preclinical to clinical experiments. Yet, there are many steps being taken to improve the quality of experimental research and translation to clinical trials.

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Physiology: Beating stroke

Cited by 5 publications

References 8 publications

Disruption of cardiac cholinergic neurons enhances susceptibility to ventricular arrhythmias

Disruption of cardiac cholinergic neurons enhances susceptibility to ventricular arrhythmias

Proarrhythmic and Torsadogenic Effects of Potassium Channel Blockers in Patients

Small molecule inhibitors in the treatment of cerebral ischemia

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