Progressive development of cardiomyopathy following altered autonomic activity in status epilepticus

Abstract

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.

Improved cardiac outcomes with combined atenolol and diazepam intervention in seizure

“…Previous work by our group demonstrated that SE resulted in an immediate elevation in sympathetic activity, leading to structural cardiac damage and seizure‐induced cardiomyopathy . Our group also confirmed that pretreatment with sympatholytics could protect the heart during seizure .…”

“…Core body temperature was maintained at 37°C throughout the surgery using a thermostatically regulated heat pad (Harvard Apparatus, Holliston, MA, USA). Transmitter implantation and electrode positioning procedures for 2‐lead EEG and ECG monitoring were performed as previously described . All animals were also implanted with a 26‐gauge intrahippocampal drug cannula (Coherent Scientific, Hilton, SA, Australia) secured into the right hippocampus (5.2 mm posterior of Bregma and 5 mm right of the midline at a depth of 5.2 mm).…”

“…Clinically, it is important that these cardiac abnormalities are attenuated, with priority given to those changes associated with risk factors for sudden cardiac death, such as tachycardia and corrected QT (QTc) prolongation . Death from cardiac injury can also occur in the postictal period and is believed to be due to an imbalance in autonomic function producing cardiovascular complications, such as lethal arrhythmias or cardiac arrest …”

Inhibition of microglial activation with minocycline at the intrathecal level attenuates sympathoexcitatory and proarrhythmogenic changes in rats with chronic temporal lobe epilepsy

“…Seizure activity is accompanied with increased sympathetic output, increased plasma noradrenaline levels, tachycardia and elevated blood pressure (Read et al, 2015;Bhandare et al, 2016a). However, our non-invasive blood pressure measurements and plasma catecholamine analysis did not reveal significant differences in MAP or plasma catecholamine levels interictally between epileptic and control rats.…”

“…However, our non-invasive blood pressure measurements and plasma catecholamine analysis did not reveal significant differences in MAP or plasma catecholamine levels interictally between epileptic and control rats. In epileptic rats, plasma catecholamine levels are reported to peak at 48 h post-seizure and then return to normal (Read et al, 2015). Differences in species, model, seizure type, seizure frequency, and duration might explain the non-significant differences in MAP and plasma catecholamines seen in epileptic and control rats.…”