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Myocardial remodeling and susceptibility to ventricular tachycardia in a model of chronic epilepsy.

ABSTRACT: Objective:Sympathetic predominance and ventricular repolarization abnormalities represent epilepsy-associated cardiac alterations and may underlie seizure-induced ventricular arrhythmias. Myocardial ion channel and electrical remodeling have been described early in epilepsy development and may contribute to ventricular repolarization abnormalities and excitability. Using the pilocarpine-induced acquired epilepsy model we sought to examine whether altered myocardial ion channel levels and electrophysiological changes also occur in animals with long-standing epilepsy. Methods:We examined myocardial adrenergic receptor and ion channel protein levels of epileptic and age-matched sham rats (9-20 months old) using western blotting. Cardiac electrical properties were examined using optical mapping ex vivo and electrophysiology in vivo. We investigated the propensity for ventricular tachycardia (VT) and the effects of ?-adrenergic blockade on ventricular electrical properties and excitability in vivo. Results:In animals with long-standing epilepsy, we observed decreased myocardial voltage-gated K+ channels Kv4.2 and Kv4.3, which are known to underlie early ventricular repolarization in rodents. Decreased ?1 and increased ?1A adrenergic receptor protein levels occurred in the myocardium of chronically epileptic animals consistent with elevated sympathetic tone. These animals exhibited many cardiac electrophysiological abnormalities, represented by longer QRS and corrected QT (QTc) intervals in vivo, slower conduction velocity ex vivo, and stimulation-induced VT. Administration of a ?-adrenergic antagonist late in epilepsy was beneficial, as the therapy shortened the QTc interval and decreased stimulation-induced VT. Significance:Our findings demonstrate that myocardial ion channel remodeling and sympathetic predominance, risk factors for increased ventricular excitability and arrhythmias, persist in chronic epilepsy. The beneficial effects of ?-adrenergic antagonist treatment late in the course of epilepsy suggest that attenuating elevated sympathetic tone may represent a therapeutic target for ameliorating epilepsy-associated cardiac morbidity.

SUBMITTER: Lai YC

PROVIDER: S-EPMC5983128 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Myocardial remodeling and susceptibility to ventricular tachycardia in a model of chronic epilepsy.

Lai Yi-Chen YC Li Na N Lawrence William W Wang Sufen S Levine Amber A Burchhardt Daniela M DM Pautler Robia G RG Valderrábano Miguel M Wehrens Xander H XH Anderson Anne E AE

Epilepsia open 20180323 2

<h4>Objective</h4>Sympathetic predominance and ventricular repolarization abnormalities represent epilepsy-associated cardiac alterations and may underlie seizure-induced ventricular arrhythmias. Myocardial ion channel and electrical remodeling have been described early in epilepsy development and may contribute to ventricular repolarization abnormalities and excitability. Using the pilocarpine-induced acquired epilepsy model we sought to examine whether altered myocardial ion channel levels and ...[more]

PMID: 29881800

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Project description:This scenario was developed to educate emergency medicine residents on the diagnosis and management of ventricular tachycardia (VT) that is refractory to single dose anti-arrhythmic management. Electrical storm, defined as three or more episodes of sustained VT, ventricular fibrillation, or appropriate shocks from an implantable cardioverter defibrillator within 24 hours,1 has a mortality rate up to 14% in the first 48 hours.2 Ventricular tachycardia may present in a heterogenous fashion, not only with stable versus unstable clinical presentations, but also with different electrocardiographic morphologies and etiologies.1 Understanding how to rapidly diagnose, treat, and utilize second or third-line treatments is vital in the setting of refractory ventricular tachycardia rather than relying on the success of first-line agents. Appreciation for what medications are readily available in your crash cart and medication dispensing cabinet is critical for timely management for refractory ventricular tachycardia. At the conclusion of the simulation session, learners will be able to: 1) identify the different etiologies of VT, including structural heart disease, acute ischemia, and acquired or congenital QT syndrome; 2) describe confounding factors of VT, such as electrolyte abnormalities and sympathetic surge; 3) describe how to troubleshoot an unsuccessful synchronized cardioversion, including checking equipment connections, increasing delivered energy, and changing pad placement; 4) compare and contrast treatments of VT based on suspected underlying etiology; 5) describe reasons to activate the cardiac catheterization lab other than occlusive myocardial infarction; and 6) identify appropriate disposition of the patient to the cardiac catheterization lab. This session was conducted using high-fidelity simulation, followed by a debriefing session and lecture on the diagnosis, differential diagnosis, and management of VT. Debriefing methods may be left to the discretion of participants, but the authors have utilized advocacy-inquiry techniques. This scenario may also be run as an oral board case. Our residents are provided a survey at the completion of the debriefing session so they may rate different aspects of the simulation, as well as provide qualitative feedback on the scenario. The local institution's simulation center's electronic feedback form is based on the Center of Medical Simulation's Debriefing Assessment for Simulation in Healthcare (DASH) Student Version Short Form3 with the inclusion of required qualitative feedback if an element was scored less than a 6 or 7. Twelve learners completed a feedback form. This session received 6 and 7 scores (consistently effective/very good and extremely effective/outstanding, respectively) other than three isolated 5 scores. The lowest average score was 6.67 for "Before the simulation, the instructor set the stage for an engaging learning experience." The highest average score was 7 for "The instructor helped me see how to improve or how to sustain good performance." The form also includes an area for general feedback about the case at the end. Illustrative examples of feedback include: "Excellent care and debrief." Specific scores are available upon request. This is a cost-effective method for reviewing VT diagnosis and management. The case may be modified for appropriate audiences, such as describing what medications may be readily available in a free-standing emergency department or pre-hospital setting. Medical simulation, ventricular tachycardia, cardiac emergencies, dysrhythmias, cardiology, emergency medicine.

Dataset Information

Myocardial remodeling and susceptibility to ventricular tachycardia in a model of chronic epilepsy.

Publications

Myocardial remodeling and susceptibility to ventricular tachycardia in a model of chronic epilepsy.

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