Epilepsy-induced heart damage and sudep risk: ion channelopathies, calcium homeostasis, and the therapeutic potential of resveratrol

Abstract

Epilepsy is a worldwide health issue associated with cardiac-related conditions and Sudden Unexpected Death in Epilepsy (SUDEP). The pathophysiology of SUDEP involves structural fibrosis of the myocardium, a calcium imbalance, and dysfunction of the autonomic nervous system. The objective of this investigation was to examine cardiac damage resulting from epilepsy triggered by the Pentylenetetrazol (PTZ) kindling rat model at a dosage of 35 mg/kg administered intraperitoneally, and to assess the therapeutic benefits of Resveratrol (RSV) at a dosage of 5 mg/kg. Cardiac function was evaluated using isolated papillary muscle recordings. Damage to the structure was assessed by Sirius Red staining and general tissue morphology. Molecular analyses encompassed qPCR (SERCA2a, CACNA1G, HCN2, CAS3/9) and immunofluorescence (SIRT1, Caspase-3, S100α) in conjunction with the total Ca 2 ⁺ content. PTZ kindling enhanced seizure severity and overall spike number on ECoG. Functionally, contractile force (CF), contractile power (AUC), and contraction/relaxation velocities (± dF/dt max ) were decreased in the PTZ group compared to the Sham group at 3, 4, and 5 Hz frequencies. Contraction duration (CT) was significantly prolonged at 5 Hz, whereas no significant change was observed in relaxation time (RT). Histopathology revealed degeneration and substantial myocardial scarring. At a molecular level, PTZ decreased SERCA 2a mRNA expression ( p p p

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