Sudden death in epilepsy: an experimental animal model

Seizure. 2006 Jul;15(5):275-87. doi: 10.1016/j.seizure.2006.02.007. Epub 2006 Mar 23.

Abstract

Introduction: The physiopathogenetic mechanisms possibly involved in sudden unexplained epileptic death (SUDEP), were investigated in the hemispherectomized rat.

Methods: For this purpose, paroxysmal activity, vagal nerve firing, systemic blood pressure (BP), pulmonary artery pressure, and ECG were simultaneously recorded in an experimental animal model of epilepsy. Recordings were performed in basal conditions and during paroxysmal activity induced by topical application of penicillin-G at hypothalamic and mesencephalic level. During the experiment were also performed hemogas analysis and at end, samples of lung tissue were processed for histology.

Results: Activation of hypothalamic (HEF) and mesencephalic (MEF) epileptic foci induced a significant increase of spontaneous vagal nerve firing that was strictly correlated to ECG impairments and hypotension. When paroxysmal activity extinguished, vagal nerve activity and cardiovascular parameters returned to basal conditions. However, in 25% of the animals, co-activation of HEF and MEF always triggered a vagal hypertone which was temporally correlated to cardiac arrhythmias, but also to hyperkalemia, acidosis, pulmonary hypertension and to animal death. Histological control in lungs of deceased animals showed an alveolar and perivessel oedema with an oedematous infiltration in the alveolar and bronchial spaces and mucous secretion. During ictal activity, comparison between survived and deceased animals showed significant differences in the incidence of ECG impairment of pulmonary artery pressures, pO2, and pCO2 pressures, and [K+], [HCO3-], and [pH], concentrations.

Discussion: A possible explanation of the above observations is discussed in relationship to SUDEP physiopathogenesis.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arrhythmias, Cardiac / physiopathology*
  • Death, Sudden / etiology*
  • Disease Models, Animal
  • Electrocardiography
  • Electroencephalography
  • Electrophysiology
  • Female
  • Hemispherectomy
  • Hypothalamus / pathology
  • Male
  • Mesencephalon / pathology
  • Penicillin G
  • Rats
  • Rats, Wistar
  • Seizures / chemically induced
  • Seizures / complications
  • Seizures / physiopathology*
  • Vagus Nerve / physiopathology*

Substances

  • Penicillin G