Cardiac dysregulation following intrahippocampal kainate-induced status epilepticus
Amber T Levine1,2,3,4, Heather A Born2,3,4, Andrew P Landstrom5
1Department of Neuroscience, Baylor College of Medicine, Houston, TX, USA.
Insights
Status epilepticus (SE) causes cardiac arrhythmias and early mortality in mice. These heart rhythm changes, including bradycardia, occur within 14 days post-SE and may signal sudden death risk.
Area of Science:
- Neuroscience
- Cardiology
- Epilepsy Research
Background:
- Status epilepticus (SE) is a neurological emergency linked to significant mortality and the development of epilepsy.
- Cardiac arrhythmias are frequently observed in patients after SE, but the underlying mechanisms and timing remain unclear.
- Early epileptogenesis, the period following SE leading to chronic epilepsy, is critical for understanding long-term outcomes.
Purpose of the Study:
- To characterize cardiac arrhythmogenesis during and between seizures in a mouse model of SE.
- To investigate the correlation between cardiac events, epileptiform activity, circadian rhythms, and survival.
- To identify potential early cardiac risk factors for mortality post-SE.
Main Methods:
- Utilized an intrahippocampal chemoconvulsant mouse model to induce SE.
- Performed continuous electrocardiography (ECG) and video electroencephalography (vEEG) monitoring for 14 days.
- Quantified heart rhythm abnormalities and correlated them with seizure activity and circadian cycles.
Main Results:
- Mice post-SE exhibited increased interictal heart rate and significant heart rhythm abnormalities (sinus pause, sinus arrhythmias) compared to controls.
- Cardiac events were more prevalent during the light cycle and did not correlate with seizure frequency or epileptiform activity.
- Early mortality was observed in SE mice, with severe bradycardia preceding death in one recorded event.
Conclusions:
- SE induces significant cardiac rhythm disturbances within 14 days, independent of seizure frequency.
- These early cardiac changes may serve as a risk indicator for sudden death in the acute phase following SE.
- Further research is warranted to explore the mechanisms linking SE, cardiac dysfunction, and mortality.
Abstract:
Status epilepticus (SE) is a prevalent disorder associated with significant morbidity, including the development of epilepsy and mortality. Cardiac arrhythmias (i.e. inappropriate sinus tachycardia and bradycardia, asystole, and atrioventricular blocks) are observed in patients following SE. We characterized ictal (during a seizure) and interictal (between seizure) cardiac arrhythmogenesis following SE using continuous electrocardiography and video electroencephalography (vEEG) recordings throughout a 14-day monitoring period in an intrahippocampal chemoconvulsant mouse model that develops epilepsy. We quantified heart rhythm abnormalities and examined whether the frequency of cardiac events correlated with epileptiform activity, circadian (light/dark) cycle, the presence of seizures, and survival during this period of early epileptogenesis (the development of epilepsy) following SE. Shortly following SE, mice developed an increased interictal heart rate and heart rhythm abnormalities (i.e. sinus pause and sinus arrhythmias) when compared to control mice. Heart rhythm abnormalities were more frequent during the light cycle and were not correlated with increased epileptiform activity or seizure frequency. Finally, SE animals had early mortality, and a death event captured during vEEG recording demonstrated severe bradycardia prior to death. These cardiac changes occurred within 14 days after SE and may represent an early risk factor for sudden death following SE.
