Repeated generalized seizures can produce calcified cardiac lesions in DBA/1 mice

Studies suggest that cardiorespiratory dysfunction likely contributes to sudden unexpected death in epilepsy (SUDEP). Seizures result in autonomic and respiratory dysfunction, leading to sympathetic hyperactivity and respiratory distress, including apnea. While the heart is vulnerable to catecholamine surges and hypoxia, it remains unknown if repetitive generalized seizures lead to cardiac damage. DBA/1 mice exhibit seizure-induced respiratory arrest (S-IRA) following generalized audiogenic seizures (AGS), which can be resuscitated using a rodent ventilator. In the current study, we induced different numbers of S-IRA episodes in DBA/1 mice and determined the association of repeated S-IRA induction with cardiac damage using histology. After repetitive induction of 18 S-IRA, calcified lesions, as revealed by calcium (Ca²⁺)-specific alizarin red staining, were observed in the ventricular myocardium in 61.5% of DBA/1 mice, which was higher compared to mice with 5 S-IRA and 1 S-IRA as well as age-matched untested control mice. The incidence of lesions in mice with 9 S-IRA was only higher than that of control mice. Only 1-2, small lesions were observed in mice with 5 S-IRA and 1 S-IRA and in control mice. Larger lesions (>2500 μm²) were observed in mice with 9 and 18 S-IRA. The incidence of larger lesions was higher in mice with 18 S-IRA (53.8%) as compared to mice with 5 S-IRA and 1 S-IRA as well as with control mice, and the incidence of larger lesions in mice with 9 S-IRA was only higher than that of control mice. Repeated induction of S-IRA in DBA/1 mice can result in calcified necrotic lesions in the ventricles of the heart, and their incidence and size are dependent on the total number of S-IRA.