Status epilepticus induces cardiac myofilament damage and increased susceptibility to arrhythmias in rats

Abstract

Status epilepticus (SE) is a seizure or series of seizures that persist for >30 min and often results in mortality. Death rarely occurs during or immediately following seizure activity, but usually within 30 days. Although ventricular arrhythmias have been implicated in SE-related mortality, the effects of this prolonged seizure activity on the cardiac function and susceptibility to arrhythmias have not been directly investigated. We evaluated myocardial damage, alterations in cardiac electrical activity, and susceptibility to experimentally induced arrhythmias produced by SE in rats. SE resulted in seizure-related increases in blood pressure, heart rate, and the first derivative of pressure, as well as modest, diffuse myocyte damage assessed by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining. Ten to twelve days following seizures, electrocardiographic recordings showed arrhythmogenic alterations in cardiac electrical activity, denoted by prolonged QT interval corrected for heart rate and QT dispersion. Finally, SE increased susceptibility to experimentally induced (intravenous aconitine) cardiac arrhythmias. These data suggest that SE produces tachycardic ischemia following the activation of the sympathetic nervous system, resulting in cardiac myofilament damage, arrhythmogenic alterations in cardiac electrical activity, and increased susceptibility to ventricular arrhythmias.

Methods for ECG Evaluation of Indicators of Cardiac Risk, and Susceptibility to Aconitine-induced Arrhythmias in Rats Following Status Epilepticus

“…This prediction is confirmed by the findings that the periods of aconitine infusion necessary to induce the experimental arrhythmias (PVC, VT, VF) observed in these studies were significantly smaller in animals following SE (Fig. 5) 27 . 2.…”

“…Fig. 4 shows that both corrected QT interval (QTc, Panel A) and QT dispersion (QTd, Panel B) are significantly increased two weeks following SE 27 . Taken together, these data predict that SE increases risk of ventricular arrhythmias.…”

Progressive development of cardiomyopathy following altered autonomic activity in status epilepticus

“…Following the 7-day behavioral study, rats (n ϭ 6/group) were administered a bolus injection of the proarrhythmogenic agent aconitine (0.5 mg/kg sc) to assess vulnerability to arrhythmias (46). The latency from aconitine administration to presentation of ECG arrhythmias was recorded in each animal.…”

“…Within the different seizure classifications, status epilepticus has the highest mortality risk, with death generally occurring within 30 days of the initial convulsant activity (39). Death often occurs in the absence of seizures and is believed to be due to an imbalance in autonomic function, resulting in altered cardiac control, electrical instability, and increased risk of lethal cardiac arrhythmias (46,51).…”

“…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.…”