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

Yi Chen Lai, Na Li, William Lawrence, Sufen Wang, Amber Levine, Daniela M. Burchhardt, Robia G. Pautler, Miguel Valderrábano, Xander H. Wehrens, Anne E. Anderson

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

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 β-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 Kv 4.2 and Kv 4.3 , which are known to underlie early ventricular repolarization in rodents. Decreased β1 and increased α1 A 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 β-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 β-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.

Original languageEnglish (US)
Pages (from-to)213-223
Number of pages11
JournalEpilepsia Open
Volume3
Issue number2
DOIs
StatePublished - 2018
Externally publishedYes

Keywords

  • Cardiac remodeling
  • Epilepsy
  • Kv
  • Ventricular tachycardia
  • β-Adrenergic blockade

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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