title: Cardiac electrographic and morphological changes following status epilepticus: effect of clonidine.
abstract: OBJECTIVE
  Status epilepticus has been increasingly associated with cardiac injury in both clinical and animal studies. Our group has previously shown that excitotoxic seizure induction results in the formation of ischaemic myocardial infarcts and loss of cardiac haemodynamic function. We hypothesised that attenuation of cardiac sympathetic/parasympathetic balance with a central presynaptic α₂ agonist, clonidine, can reduce the development of interictal ECG and ventricular morphological changes resulting from kainic acid (KA; 10mg/kg) induced status epilepticus in a conscious rat model.
  
  
  METHODS
  Using simultaneous ECG and electrocorticogram (ECoG) radiotelemetry, animals were randomised into saline controls, saline-pretreated KA and clonidine (100 μg/kg, b.i.d.)-pretreated KA groups. Baseline ECG, ECoG and behavioural score recordings were acquired in conscious animals for 2h post-KA administration.
  
  
  RESULTS
  Bradycardia and low level seizure activity occurred immediately following KA administration. As seizure activity (ECoG spiking and high level seizure behavioural scoring) progressively increased, tachycardia developed. Both QTc prolongation and T wave amplitude were transiently but significantly increased. Clonidine treatment attenuated seizure activity, increased the latency to onset of seizure behaviour and reduced seizure-induced changes in heart rate, QTc interval, and T wave amplitude. Histological examination of the ventricular myocardium revealed hypercontraction band necrosis, inflammatory cell infiltration, and oedema at 48 h post-KA. In contrast, clonidine-treatment in seizure animals preserved tissue integrity and structure.
  
  
  CONCLUSIONS
  These results demonstrate that KA-induced seizures are associated with altered ECG activity and cardiac structural pathology. We suggest that pharmacological modulation of sympathetic/parasympathetic activity in status epilepticus provides a promising therapeutic approach to reduce seizure-induced cardiomyopathy.
authors.affiliation: Department of Pharmacology and Toxicology, University of Otago School of Medical Sciences, Dunedin, New Zealand.
authors.forename: Morgayn I
authors.initials: MI
authors.lastname: Read
authors.affiliation: Department of Pharmacology and Toxicology, University of Otago School of Medical Sciences, Dunedin, New Zealand.
authors.forename: Anastasia A
authors.initials: AA
authors.lastname: Andreianova
authors.affiliation: Department of Pharmacology and Toxicology, University of Otago School of Medical Sciences, Dunedin, New Zealand.
authors.forename: Joanne C
authors.initials: JC
authors.lastname: Harrison
authors.affiliation: Department of Pharmacology and Toxicology, University of Otago School of Medical Sciences, Dunedin, New Zealand.
authors.forename: Chelsea S
authors.initials: CS
authors.lastname: Goulton
authors.affiliation: Department of Pharmacology and Toxicology, University of Otago School of Medical Sciences, Dunedin, New Zealand. Electronic address: ivan.sammut@otago.ac.nz.
authors.forename: Ivan A
authors.initials: IA
authors.lastname: Sammut
authors.affiliation: Department of Pharmacology and Toxicology, University of Otago School of Medical Sciences, Dunedin, New Zealand.
authors.forename: D Steven
authors.initials: DS
authors.lastname: Kerr
mesh_terms: D000818:Animals; D003000:Clonidine / Q000494:pharmacology* / Q000627:therapeutic use*; D004311:Double-Blind Method; D004562:Electrocardiography / Q000187:drug effects* / Q000379:methods; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D009203:Myocardial Infarction / Q000209:etiology / Q000473:pathology; D009206:Myocardium / Q000473:pathology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013226:Status Epilepticus / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D016896:Treatment Outcome
chemical_list: D003000:Clonidine
keywords: AMPA; Cardiomyopathy; ECoG; H&E; HR; KA; MSB; Martius scarlet blue; QT prolongation; SE; Status epilepticus; Sympatholytic; WDS; b.p.m.; beats per minute; electrocorticogram; haematoxylin-eosin; heart rate; kainic acid; sc; status epilepticus; sub-cutaneous; wet dog shakes; α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate