title: Cardiac phenomena during kainic-acid induced epilepsy and lamotrigine antiepileptic therapy.
abstract: BACKGROUND
  Pathologic ECG events are known to accompany seizures and to persist in several chronic epilepsy syndromes. The contribution of antiepileptic drugs (AEDs) to these events and the implications in the etiology of sudden-unexpected death in epilepsy (SUDEP) continue to be a matter of debate. We therefore investigated cardiac parameters during kainic-acid (KA) induced experimental epilepsy and antiepileptic treatment with lamotrigine (LTG).
  
  
  METHODS
  Epilepsy was induced in seven C57Bl/6 mice by injections of KA (20 mg/kg) on days 1 and 5, which produced severe acute seizures and spontaneous seizures 10 days later. Treatment with LTG (30 mg/kg) was initiated on day 11 and repeated on day 12. Continuous ECGs and ECoGs were collected telemetrically from freely moving mice.
  
  
  RESULTS
  Mice displayed pre-ictal but not ictal tachycardia. The squared coefficient of variation (SCV) of R-R intervals was significantly elevated 30s before and during seizures compared to control conditions. LTG produced a significant reversible increase in SCV and LF/HF ratio during slow-wave sleep (SWS), potentially indicative of sympatho-vagal imbalance during this state of vigilance, in which epileptic patients are known to be particularly vulnerable to SUDEP.
  
  
  CONCLUSIONS
  The KA model used in this study permits the investigation of cardiac phenomena during epilepsy, as it features many effects found in human epileptic patients. Increased LF/HF, a known risk factor for cardiac disease, which is often found in epileptic patients, was observed as a side-effect of LTG treatment during SWS, suggesting that LTG may promote imbalance of the autonomous nervous system in epileptic mice.
authors.affiliation: Institute for Neurophysiology, University of Cologne, Robert-Koch Straße 39, D-50931 Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), University of Cologne, Robert-Koch Straße 39, D-50931 Cologne, Germany; Department of Neurosurgery, University Hospital, Heinrich-Heine-University, Düsseldorf, Moorenstraße 5, D-40225 Düsseldorf, Germany. Electronic address: Maxine.dibue@med.uni-duesseldorf.de.
authors.forename: Maxine
authors.initials: M
authors.lastname: Dibué
authors.affiliation: Institute for Neurophysiology, University of Cologne, Robert-Koch Straße 39, D-50931 Cologne, Germany; Department of Neurosurgery, University Hospital, Heinrich-Heine-University, Düsseldorf, Moorenstraße 5, D-40225 Düsseldorf, Germany.
authors.forename: Marcel A
authors.initials: MA
authors.lastname: Kamp
authors.affiliation: Institute for Neurophysiology, University of Cologne, Robert-Koch Straße 39, D-50931 Cologne, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Neumaier
authors.affiliation: Department of Neurosurgery, University Hospital, Heinrich-Heine-University, Düsseldorf, Moorenstraße 5, D-40225 Düsseldorf, Germany.
authors.forename: Hans-Jakob
authors.initials: HJ
authors.lastname: Steiger
authors.affiliation: Department of Neurosurgery, University Hospital, Heinrich-Heine-University, Düsseldorf, Moorenstraße 5, D-40225 Düsseldorf, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Hänggi
authors.affiliation: Institute for Neurophysiology, University of Cologne, Robert-Koch Straße 39, D-50931 Cologne, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Hescheler
authors.affiliation: Institute for Neurophysiology, University of Cologne, Robert-Koch Straße 39, D-50931 Cologne, Germany.
authors.forename: Toni
authors.initials: T
authors.lastname: Schneider
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D003645:Death, Sudden / Q000209:etiology; D004562:Electrocardiography; D004827:Epilepsy / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology*; D007608:Kainic Acid; D000077213:Lamotrigine; D051379:Mice; D012307:Risk Factors; D013610:Tachycardia / Q000503:physiopathology*; D014227:Triazines / Q000627:therapeutic use*
chemical_list: D000927:Anticonvulsants; D014227:Triazines; D007608:Kainic Acid; D000077213:Lamotrigine
keywords: Electrocardiography; Electrocorticography; Kainic-acid; SUDEP; Sleep; Sympatho-vagal imbalance