title: Atenolol offers better protection than clonidine against cardiac injury in kainic acid-induced status epilepticus.
abstract: OBJECTIVE
  Status epilepticus is increasingly associated with cardiac injury in both clinical and animal studies. The current study examined ECG activity for up to 48 h following kainic acid (KA) seizure induction and compared the potential of atenolol and clonidine to attenuate this cardiac pathology.
  
  
  METHODS
  Sprague-Dawley rats (male, 300-350 g) were implanted with ECG and electrocorticogram electrodes to allow simultaneous telemetric recordings of cardiac and cortical responses during and after KA-induced seizures. Animals were randomized into saline controls, and saline vehicle-, clonidine- or atenolol-pretreated KA groups.
  
  
  RESULTS
  KA administration in the saline-pretreated group produced an immediate bradycardic response (maximal decrease of 28 ± 6%), coinciding with low-level seizure activity. As high-level seizure behaviours and EEG spiking increased, tachycardia also developed, with a maximum heart rate increase of 38 ± 7% coinciding with QTc prolongation and T wave elevation. Both clonidine and atenolol pretreatment attenuated seizure activity and reduced KA-induced changes in heart rate, QTc interval and T wave amplitude observed during both bradycardic and tachycardic phases in saline-pretreated KA animals. Clonidine, however, failed to reduce the power of EEG frequencies. Atenolol and to a lesser extent clonidine attenuated the cardiac hypercontraction band necrosis, inflammatory infiltration, and oedema at 48 h after KA, relative to the saline-KA group.
  
  
  CONCLUSIONS
  Severe seizure activity in this model was clearly associated with altered ECG activity and cardiac pathology. We suggest that modulation of sympathetic activity by atenolol provides a promising cardioprotective approach in status epilepticus.
authors.affiliation: Department of Pharmacology, University of Otago School of Medical Sciences, Dunedin, New Zealand.
authors.forename: M I
authors.initials: MI
authors.lastname: Read
authors.affiliation: Department of Pharmacology, University of Otago School of Medical Sciences, Dunedin, New Zealand.
authors.forename: J C
authors.initials: JC
authors.lastname: Harrison
authors.affiliation: Department of Pharmacology, University of Otago School of Medical Sciences, Dunedin, New Zealand.
authors.forename: D S
authors.initials: DS
authors.lastname: Kerr
authors.affiliation: Department of Pharmacology, University of Otago School of Medical Sciences, Dunedin, New Zealand.
authors.forename: I A
authors.initials: IA
authors.lastname: Sammut
mesh_terms: D000818:Animals; D001262:Atenolol / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D003000:Clonidine / Q000627:therapeutic use*; D004562:Electrocardiography; D004569:Electroencephalography; D006335:Heart Injuries / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D007608:Kainic Acid; D008297:Male; D009206:Myocardium / Q000473:pathology; D017207:Rats, Sprague-Dawley; D013226:Status Epilepticus / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology
chemical_list: D002316:Cardiotonic Agents; D001262:Atenolol; D003000:Clonidine; D007608:Kainic Acid