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dc.contributor.advisorSammut, Ivan Andrew
dc.contributor.authorMcCann, Dominic Michael
dc.date.available2015-02-24T19:46:21Z
dc.date.copyright2015
dc.identifier.citationMcCann, D. M. (2015). Comparison of Cardioprotective Therapy with Atenolol and Diltiazem in Seizure-Induced Cardiomyopathy (Thesis, Master of Science). University of Otago. Retrieved from http://hdl.handle.net/10523/5474en
dc.identifier.urihttp://hdl.handle.net/10523/5474
dc.description.abstractSeizure-induced autonomic dysregulation is frequently linked with the development of cardiac abnormalities. The current study examined the therapeutic effects of pre- and post-treatment with atenolol or diltiazem in a model of seizure-induced cardiomyopathy. Male Sprague-Dawley rats (320-350g) were implanted with a telemetric transmitter to simultaneous record EEG/ECG and an intrahippocampal (ih.) drug cannula to allow delivery of kainic acid (KA; 2 nmol, 1 uL/min) directly into the hippocampus. Seizure behavioural activity was assessed using a 0-5 point modified Racine scale. Pre-treatment animal groups (n=4) were administered saline, atenolol (5 mg/kg) or diltiazem (2.5 mg/kg, bid.) subcutaneously for 3 days prior to KA-seizure induction and for a further 48 hours post-seizure. In comparison, post-treatment animals received saline, atenolol (5 mg/kg) or diltiazem (5 mg/kg bid.) subcutaneously 60 min post-KA and for the remaining 7 days. Induction of seizures in saline dosed (saline-KA) animals resulted in increased mean heart rate (HR; 17%) over the immediate 3 hour recording period, as well as a concurrent rise in systolic blood pressure (SBP; 27%) at 1 hour post induction. Pre- and post-treatment with atenolol significantly reduced seizure-induced ECG changes, including HR and QTc interval. Animals pre-treated with diltiazem showed a reduction in ictal-induced tachycardia at 1 hour whilst post-treatment with diltiazem only reduced the tachycardia seen at the end of the 3 hour ECG recording period. Post-treatment with both atenolol and diltiazem returned SBP to baseline levels. Interestingly, seizure behavioural scores were significantly reduced in atenolol treated rats. Histological investigations also showed that treatment with these cardiovascular drugs reduced apoptotic cell death, inflammatory cell infiltration and the level of structural cardiac damage, including fibrosis and oedema. This finding is of significance as the development of these structural abnormalities in the myocardial tissue can alter cardiac conduction and increase the risk of arrhythmia. Administration of the pro-arrhythmogenic agent aconitine (0.5 mg/kg sc.) was used to show a reduction in the time to arrhythmia onset as a consequence of seizure in KA-saline animals versus naïve saline control. Intervention with both cardiac drugs in the seizure animals negated the significant effect of seizure on cardiac susceptibility to arrhythmia. The current findings suggest that pharmacological intervention with atenolol or diltiazem can provide protection from seizure-induced cardiac injury and therefore should be considered as an adjunct therapy in severe epilepsy.
dc.format.mimetypeapplication/pdf
dc.language.isoen
dc.publisherUniversity of Otago
dc.rightsAll items in OUR Archive are provided for private study and research purposes and are protected by copyright with all rights reserved unless otherwise indicated.
dc.subjectseizure
dc.subjectcardiac
dc.subjectkainic-acid
dc.subjectECG
dc.subjecttachycardia
dc.subjectQTc prolongation
dc.subjectfibrosis
dc.subjectatenolol
dc.subjectdiltiazem
dc.subjectcardiomyopathy
dc.titleComparison of Cardioprotective Therapy with Atenolol and Diltiazem in Seizure-Induced Cardiomyopathy
dc.typeThesis
dc.date.updated2015-02-24T06:05:06Z
dc.language.rfc3066en
thesis.degree.disciplinePharmacology & Toxicology
thesis.degree.nameMaster of Science
thesis.degree.grantorUniversity of Otago
thesis.degree.levelMasters
otago.openaccessOpen
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