Does epilepsy cause a secondary cardiac channelopathy?
- Research Opportunity
- PhD, Masters by Research, Honours
- Project Status
- Medicine and Radiology
- Royal Melbourne Hospital
|Dr Kim Powellfirstname.lastname@example.org||Personal web page|
|Prof Terry O'Brienemail@example.com||Personal web page|
People with epilepsy are at a higher risk of death than the general population. People with epilepsy may die suddenly without an obvious pathologic cause for death. Such deaths are termed Sudden Unexpected Death in EPilepsy (SUDEP), and this is the major clinical problem facing epilepsy patients, accounting for 17-38% of all epilepsy related deaths. Basic research investigating the causal mechanisms underlying SUDEP is lacking. Alterations in function or expression of ion channels expressed in both cerebral and cardiac tissue represent strong candidate mechanisms for SUDEP - defects in membrane excitability could predispose an individual to a dual phenotype of epilepsy and cardiac arrhythmia. In both a genetic and an acquired animal model of epilepsy we have identified altered cardiac electrophysiological function with an associated down-regulation of the cardiac pacemaker HCN2 channel. Based on this data we have hypothesised that the development of epilepsy itself can results in secondary changes in cardiac ion channel expression and function that could contribute to an increased risk of cardiac arrhythmias and therefore SUDEP.
To investigate whether patients with chronic epilepsy have alterations in cardiac electrophysiology and ion channel expression compared to matched non-epileptic control subjects.
This will be investigated by examining cardiac tissue from patients with chronic epilepsy collected during open heart surgery at the Royal Melbourne Hospital and Melbourne Private. This tissue collected will be atrial muscle, which is routinely excised, and discarded as part of the routine cannulation of patients that are being placed on cardiopulmonary bypass for cardiac surgery. These patients would be identified by using a screening questionnaire given to all patients during the pre-admission clinic assessment. Identified patients will then be given a more detailed interview collecting data about their epilepsy syndrome, aetiology, duration, seizure frequency, and medication history. Control subjects will be patients without a history of epilepsy matched to the epilepsy patients for age, sex, cardiac disease status in a ratio of 1:3 (i.e. three controls for each patient with epilepsy). The mRNA and protein levels for the ion channels, HCN2 and 4 channels, which are expressed both in the hearth and the brain will be measured, and compared between the epilepsy and control patients. The patients’ ECG recordings will also be compared for significant electrophysiological difference. Any significant molecular or electrophysiological changes identified will be correlated with the epilepsy syndrome (i.e. genetic vs. acquired), the duration of epilepsy and the seizure frequency. Parrellel studies are being undertaken in animal models of chronic epilepsy to enable the mechanisms causing the epilepsy-associated cardiac changes to be better elucidated.
This study has the potential to identify the mechanism responsible for epilepsy-associated cardiac dysfunction and thereby provide an opportunity to target interventions that can prevent the cardiac dysfunction, and mitigate the risk of SUDEP.
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