Document Detail


Cardiac electrographic and morphological changes following status epilepticus: effect of clonidine.
MedLine Citation:
PMID:  24139618     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: 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.
CONCLUSION: 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:
Morgayn I Read; Anastasia A Andreianova; Joanne C Harrison; Chelsea S Goulton; Ivan A Sammut; D Steven Kerr
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Publication Detail:
Type:  Journal Article     Date:  2013-09-25
Journal Detail:
Title:  Seizure     Volume:  23     ISSN:  1532-2688     ISO Abbreviation:  Seizure     Publication Date:  2014 Jan 
Date Detail:
Created Date:  2013-12-23     Completed Date:  2014-08-24     Revised Date:  2014-10-21    
Medline Journal Info:
Nlm Unique ID:  9306979     Medline TA:  Seizure     Country:  England    
Other Details:
Languages:  eng     Pagination:  55-61     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Animals
Clonidine / pharmacology*,  therapeutic use*
Double-Blind Method
Electrocardiography / drug effects*,  methods
Heart / drug effects,  physiopathology
Male
Myocardial Infarction / etiology,  pathology
Myocardium / pathology*
Random Allocation
Rats
Rats, Sprague-Dawley
Status Epilepticus / drug therapy*,  pathology,  physiopathology*
Treatment Outcome
Chemical
Reg. No./Substance:
MN3L5RMN02/Clonidine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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