Dynamic alterations in cardiac autonomic regulation during recurrent generalized seizures

Epileptic seizures are associated with cardiovascular disturbances, yet how cardiac autonomic regulation changes across repeated seizures remains unclear. Here, using a pentylenetetrazol-induced murine model, we combined ECG telemetry, heart rate variability (HRV) analysis, pharmacological intervention, optical mapping, and brainstem patch-clamp recordings to characterize seizure-associated autonomic responses. Acute seizures produced transient bradyarrhythmias and increased HRV indices that were attenuated by muscarinic blockade. In contrast, repeated seizures reduced HRV and decreased the excitability of cardiac vagal neurons in the nucleus ambiguus, whereas optical mapping detected no significant intrinsic myocardial electrophysiological abnormalities. Together, these findings identify dynamic, stage-dependent alterations in cardiac autonomic regulation during recurrent generalized seizures, with distinct autonomic changes observed following acute and repeated seizure exposure.