Progressive development of cardiomyopathy following altered autonomic activity in status epilepticus.
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 μl/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 ± 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 < 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.
Department of Pharmacology, University of Otago School of Medical Sciences, Dunedin, New Zealand.
Morgayn I
MI
Read
Department of Pharmacology, University of Otago School of Medical Sciences, Dunedin, New Zealand.
Dominic M
DM
McCann
Department of Pharmacology, University of Otago School of Medical Sciences, Dunedin, New Zealand.
Rebecca N
RN
Millen
Department of Pharmacology, University of Otago School of Medical Sciences, Dunedin, New Zealand.
Joanne C
JC
Harrison
Department of Pharmacology, University of Otago School of Medical Sciences, Dunedin, New Zealand.
D Steven
DS
Kerr
Department of Pharmacology, University of Otago School of Medical Sciences, Dunedin, New Zealand ivan.sammut@otago.ac.nz.
Ivan A
http://orcid.org/0000-0002-9217-9452
IA
Sammut
D000157:Aconitine / Q000633:toxicity; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000503:physiopathology; D001341:Autonomic Nervous System / Q000503:physiopathology; D001794:Blood Pressure; D009202:Cardiomyopathies / Q000473:pathology / Q000503:physiopathology; D002311:Cardiomyopathy, Dilated / Q000097:blood / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D005355:Fibrosis; D006339:Heart Rate; D007608:Kainic Acid / Q000633:toxicity; D008297:Male; D009206:Myocardium / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000473:pathology*; D009638:Norepinephrine / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D013226:Status Epilepticus / Q000097:blood / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology*; D013318:Stroke Volume / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D014617:Vacuoles / Q000473:pathology; D061585:Voltage-Gated Sodium Channel Agonists / Q000633:toxicity
D018690:Excitatory Amino Acid Agonists; D061585:Voltage-Gated Sodium Channel Agonists; D007608:Kainic Acid; D009638:Norepinephrine; D000157:Aconitine
arrhythmias; autonomic; electrocardiogram; seizure; sympathetic