Cardioprotective effects of amiodarone in a rat model of epilepsy-induced cardiac dysfunction

Clin Exp Pharmacol Physiol. 2022 Mar;49(3):406-418. doi: 10.1111/1440-1681.13615. Epub 2021 Dec 1.

Abstract

Cardiac dysfunction is one of the leading causes of death in epilepsy. The anti-arrhythmic drug, amiodarone, is under investigation for its therapeutic effects in epilepsy. We aimed to evaluate the possible effects of amiodarone on cardiac injury during status epilepticus, as it can cause prolongation of the QT interval. Five rat groups were enrolled in the study; three control groups (1) Control, (2) Control-lithium and (3) Control-Amio, treated with 150 mg/kg/intraperitoneal amiodarone, (4) Epilepsy model, induced by sequential lithium/pilocarpine administration, and (5) the epilepsy-Amio group. The model group expressed a typical clinical picture of epileptiform activity confirmed by the augmented electroencephalogram alpha and beta spikes. The anticonvulsive effect of amiodarone was prominent, it diminished (p < 0.001) the severity of seizures and hence, deaths and reduced serum noradrenaline levels. In the model group, the electrocardiogram findings revealed tachycardia, prolongation of the corrected QT (QTc) interval, depressed ST segments and increased myocardial oxidative stress. The in-vitro myocardial performance (contraction force and - (df/dt)max ) was also reduced. Amiodarone decreased (p < 0.001) the heart rate, improved ST segment depression, and myocardial contractility with no significant change in the duration of the QTc interval. Amiodarone preserved the cardiac histological structure and reduced the myocardial injury markers represented by serum Troponin-I, oxidative stress and IL-1. Amiodarone pretreatment prevented the anticipated cardiac injury induced during epilepsy. Amiodarone possessed an anticonvulsive potential, protected the cardiac muscle and preserved its histological architecture. Therefore, amiodarone could be recommended as a protective therapy against cardiac dysfunction during epileptic seizures with favourable effect on seizure activity.

Keywords: amiodarone; anticonvulsant; electrocardiography; epilepsy; myocardial performance; oxidation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Adjuvants, Immunologic / toxicity
  • Amiodarone / therapeutic use*
  • Animals
  • Anti-Arrhythmia Agents / therapeutic use*
  • Biomarkers / blood
  • Epilepsy / chemically induced
  • Epilepsy / complications*
  • Glutathione / blood
  • Heart Diseases / drug therapy*
  • Heart Diseases / etiology*
  • Interleukin-1 / metabolism
  • Lithium Chloride / administration & dosage
  • Lithium Chloride / toxicity
  • Male
  • Malondialdehyde / blood
  • Muscarinic Agonists / administration & dosage
  • Muscarinic Agonists / toxicity
  • Myocardial Contraction / drug effects
  • Pilocarpine / administration & dosage
  • Pilocarpine / toxicity
  • Rats
  • Rats, Wistar
  • Superoxide Dismutase / blood
  • Troponin I / blood

Substances

  • Adjuvants, Immunologic
  • Anti-Arrhythmia Agents
  • Biomarkers
  • Interleukin-1
  • Muscarinic Agonists
  • Troponin I
  • Pilocarpine
  • Malondialdehyde
  • Superoxide Dismutase
  • Lithium Chloride
  • Glutathione
  • Amiodarone

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