Autonomic and cellular mechanisms mediating detrimental cardiac effects of status epilepticus

Abstract

Prolonged seizure activity (status epilepticus; SE) can result in increased susceptibility to lethal ventricular arrhythmias for an extended period of time following seizure termination. SE is accompanied by acute, intense activation of the sympathetic nervous system (SymNS) and results in myocyte myofilament damage, arrhythmogenic alterations in cardiac electrical activity, and increased susceptibility to ventricular arrhythmias. However, the mechanisms mediating the changes in cardiac function, and the specific arrhythmogenic substrate produced during SE are unknown. To determine if detrimental cardiac effects of SE are mediated by SymNS stimulation of the heart, we examined the effects of B-adrenergic blockade (atenolol) during seizure activity on blood pressure, heart rate, myocyte myofilament injury (cardiac troponin I, cTnI), electrocardiographic activity, and susceptibility to arrhythmias. Furthermore, we determined if SE was associated with altered expression of the Kv4.x potassium channels, which are critical for action potential repolarization and thereby contribute significantly to normal cardiac electrical activity. Lithium-pilocarpine induced SE was associated with acute tachycardia, hypertension, and cardiomyocyte damage. Arrhythmogenic alterations in cardiac electrical activity accompanied by increased susceptibility to experimentally induced arrhythmias were evident during the first 2 wks following SE. Both were prevented by atenolol treatment during seizures. Furthermore, one and two weeks after SE, myocyte ion channel remodeling, characterized by a decreased expression of cardiac Kv4.2 potassium channels, was evident. These data suggest that the cardiac effects of prolonged and intense SymNS activation during SE induce myofilament damage and downregulation of Kv4.2 channels, which alter cardiac electrical activity and increase susceptibility to lethal arrhythmias.

Prognostication of Electrocardiographic Changes With Status Epilepticus in African American Population

“…This can only be determined by systematically examining outcomes resulting from national clinical pathways and randomized controlled trials [5]. It has been proven that SE causes intense activation of the sympathetic nervous system and results in myocyte myofilament damage, arrhythmogenic alterations in cardiac electrical activity and increased susceptibility to ventricular arrhythmias [19,20], yet the prognostic value of these cardiac changes has yet to be determined.…”

Progressive development of cardiomyopathy following altered autonomic activity in status epilepticus

“…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.…”

Cerebrogenic cardiopathy

“…In a rat epilepsy model increased cardiovascular sympathetic tone was associated with reduced Kv4.2 levels (a channel crucial for repolarization), increased QTc dispersion and Troponin I elevation, these effects being blocked by atenolol [76]. The exact cause of this reduction is unclear, however in vitro studies indicate that CaMKII (activated by β-receptors) phosphorylates Kv4.2 potassium channels and changes the amount present in the cell membrane [77].…”