Seizures following hippocampal kindling induce QT interval prolongation and increased susceptibility to arrhythmias in rats

Bealer, Steven L.; Little, Jason G.

doi:10.1016/j.eplepsyres.2013.01.002

Cited by 30 publications

(27 citation statements)

References 19 publications

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“…Recurrent seizures in kindled rats can cause QT prolongation and increased susceptibility to seizure-induced arrhythmias (Bealer and Little, 2013). Clinically significant ictal QTc prolongation and recurrent transient third degree AV conduction block have been observed during epileptic seizures (Brotherstone et al, 2010;Seyal et al, 2011;Surges et al, 2009b).…”

Section: Ictal Repolarization Abnormalitiesmentioning

confidence: 99%

Cardiac and Autonomic Mechanisms Contributing to SUDEP

Bermeo‐Ovalle

Kennedy

Schuele

2015

Journal of Clinical Neurophysiology

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Sudden unexpected death in epilepsy is likely caused by a cascade of events affecting the vegetative nervous system leading to cardiorespiratory failure and death. Multiple genetic, electrophysiological, neurochemical, and pharmacological cardiac alterations have been associated with epilepsy, which can affect autonomic regulation of the heart and predispose patients to sudden unexpected death in epilepsy. These cardiac and autonomic changes are more frequently seen in patients with longstanding and medication refractory epilepsy and may be a prerequisite for sudden unexpected death in epilepsy. Cardiac changes are also observed within the immediate periictal period in patients with and without preexisting cardiac pathology and could be the tipping point in the cascade of events compromising autonomic, respiratory, and cardiac function during an epileptic convulsion. Better understanding if and how these cardiac alterations can make a particular individual with epilepsy more susceptible to sudden unexpected death in epilepsy will hopefully lead us to more effective preventative strategies.

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Section: Ictal Repolarization Abnormalitiesmentioning

confidence: 99%

Cardiac and Autonomic Mechanisms Contributing to SUDEP

Bermeo‐Ovalle

Kennedy

Schuele

2015

Journal of Clinical Neurophysiology

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“…In contrast to earlier studies (3,4,38,46,47,62), this investigation used implantable transmitters in con-scious (nonanesthetized) animals to simultaneously assess cardiac function and encephalographic activity during and following seizure activity. Using an adaptation of a previously validated protocol of excitotoxic seizure induction (73), intrahippocampal KA administration was employed to produce seizures while excluding any direct systemic effects of the excitotoxin.…”

mentioning

confidence: 99%

Progressive development of cardiomyopathy following altered autonomic activity in status epilepticus

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McCann

Millen

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

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Seizures are associated with altered autonomic activity, which has been implicated in the development of cardiac dysfunction and structural damage. This study aimed to investigate the involvement of the autonomic nervous system in seizure-induced cardiomyopathy. Male Sprague-Dawley rats (320 -350 g) were implanted with EEG/ECG electrodes to allow simultaneous telemetric recordings during seizures induced by intrahippocampal (2 nmol, 1 l/min) kainic acid and monitored for 7 days. Seizure activity occurred in conjunction with increased heart rate (20%), blood pressure (25%), and QTc prolongation (15%). This increased sympathetic activity was confirmed by the presence of raised plasma noradrenaline levels at 3 h post-seizure induction. By 48 h post-seizure induction, sympathovagal balance was shifted in favor of sympathetic dominance, as indicated by both heart rate variability (LF/HF ratio of 3.5 Ϯ 1.0) and pharmacological autonomic blockade. Functional cardiac deficits were evident at 7 and 28 days, as demonstrated by echocardiography showing a decreased ejection fraction (14% compared with control, P Ͻ 0.05) and dilated cardiomyopathy present at 28 days following seizure induction. Histological changes, including cardiomyocyte vacuolization, cardiac fibrosis, and inflammatory cell infiltration, were evident within 48 h of seizure induction and remained present for up to 28 days. These structural changes most probably contributed to an increased susceptibility to aconitine-induced arrhythmias. This study confirms that prolonged seizure activity results in acute and chronic alterations in cardiovascular control, leading to a deterioration in cardiac structure and function. This study further supports the need for modulation of sympathetic activity as a promising therapeutic approach in seizure-induced cardiomyopathy.

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“…The rat model of epilepsy used in this study faithfully reproduces these cardiac arrhythmias. 8,9 Editorial see p 769…”

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confidence: 99%

Prolongation of Action Potential Duration and QT Interval During Epilepsy Linked to Increased Contribution of Neuronal Sodium Channels to Cardiac Late Na ⁺ Current

Biet

Morin

Lessard‐Beaudoin

et al. 2015

Circ: Arrhythmia and Electrophysiology

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Background-Arrhythmias associated with QT prolongation on the ECG often lead to sudden unexpected death in epilepsy.The mechanism causing a prolongation of the QT interval during epilepsy remains unknown. Based on observations showing an upregulation of neuronal sodium channels in the brain during epilepsy, we tested the hypothesis that a similar phenomenon occurs in the heart and contributes to QT prolongation by altering cardiac sodium current properties (I Na ). Methods and Results-We used the patch clamp technique to assess the effects of epilepsy on the cardiac action potential and I Na in rat ventricular myocytes. Consistent with QT prolongation, epileptic rats had longer ventricular action potential durations attributable to a sustained component of I Na (I NaL ). The increase in I NaL was because of a larger contribution of neuronal Na channels characterized by their high sensitivity to tetrodotoxin. As in the brain, epilepsy was associated with an enhanced expression of the neuronal isoform Na V 1.1 in cardiomyocyte. Epilepsy was also associated with a lower I Na activation threshold resulting in increased cell excitability. Conclusions-This is the first study correlating increased expression of neuronal sodium channels within the heart to epilepsy-related cardiac arrhythmias. This represents a new paradigm in our understanding of cardiac complications related to epilepsy. (Circ Arrhythm Electrophysiol. 2015;8:912-920.

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Seizures following hippocampal kindling induce QT interval prolongation and increased susceptibility to arrhythmias in rats

Cited by 30 publications

References 19 publications

Cardiac and Autonomic Mechanisms Contributing to SUDEP

Cardiac and Autonomic Mechanisms Contributing to SUDEP

Progressive development of cardiomyopathy following altered autonomic activity in status epilepticus

Prolongation of Action Potential Duration and QT Interval During Epilepsy Linked to Increased Contribution of Neuronal Sodium Channels to Cardiac Late Na ⁺ Current

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Seizures following hippocampal kindling induce QT interval prolongation and increased susceptibility to arrhythmias in rats

Cited by 30 publications

References 19 publications

Cardiac and Autonomic Mechanisms Contributing to SUDEP

Cardiac and Autonomic Mechanisms Contributing to SUDEP

Progressive development of cardiomyopathy following altered autonomic activity in status epilepticus

Prolongation of Action Potential Duration and QT Interval During Epilepsy Linked to Increased Contribution of Neuronal Sodium Channels to Cardiac Late Na + Current

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Prolongation of Action Potential Duration and QT Interval During Epilepsy Linked to Increased Contribution of Neuronal Sodium Channels to Cardiac Late Na ⁺ Current