|Institution:||University of Otago|
|Keywords:||Kainic acid; cardiomyopathy; seizure; KA-induced; KA-induced seizure; peripheral cardiac receptors; clonidine; atenolol|
|Full text PDF:||http://hdl.handle.net/10523/5678|
Single subcutaneous administration of Kainic acid (KA) in the rat produces significant levels of seizure activity, including head tremors, salivation and tonic-clonic convulsions. Using electrophysiological quantitative techniques which measure electroencephalographic (EEG) as well as electrocardiographic (ECG) trace activity following KA administration, the effects of seizure activity on the function of the heart were assessed over a 48 hour period. In addition, histopathological analysis was carried out in order to determine whether the ongoing seizure activity produced significant changes in ventricular myocardium indicative of irreversible cardiomyopathy. In order to determine the potential mechanism of action of KA-induced cardiac damage, a further two animal groups were examined. The groups consisted of animals pretreated with either atenolol or clonidine. The two different drugs were used in order to isolate systems involved in cardiac damage, where atenolol acts specifically in the periphery, while clonidine is known to act in the central nervous system. Analysis of EEG and concomitant ECG traces, during and following seizure activity demonstrated significant changes in heart rate (HR) as well as associated HR parameters compared to baseline. Upon further histological observations it was apparent that at 48 hours following KA administration, ischaemia was present as well as evidence of inflammatory cell infiltration, tissue tearing and oedema compared to saline treated animals. Further assessment of pretreated animal groups lead to the conclusion that atenolol was not protective against KA-induced cardiac damage in the rat while clonidine was. These findings propose that the mechanism by which KA-induced seizure activity results in cardiomyopathy is through modulation of brain centres associated with cardiac control, as opposed to KA binding to peripheral cardiac receptors as previously suggested.