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

Haiting Zhao; Honghai Zhang; Frederick J Schoen; Steven C Schachter; Hua-Jun Feng

doi:10.1016/j.yebeh.2019.04.010

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

Epilepsy Behav. 2019 Jun:95:169-174. doi: 10.1016/j.yebeh.2019.04.010. Epub 2019 May 4.

Authors

Haiting Zhao¹, Honghai Zhang², Frederick J Schoen³, Steven C Schachter⁴, Hua-Jun Feng⁵

Affiliations

¹ Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China.
² Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Department of Anesthesia, Hangzhou First People's Hospital, Nanjing Medical University, Hangzhou 310006, China.
³ Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
⁴ Departments of Neurology, Beth Israel Deaconess Medical Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02215, USA.
⁵ Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. Electronic address: feng.huajun@mgh.harvard.edu.

PMID: 31063933
DOI: 10.1016/j.yebeh.2019.04.010

Abstract

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.

Keywords: Calcification; Calcified lesions; Heart; Histology; Repeated seizures; SUDEP.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Calcinosis / etiology*
Disease Models, Animal
Heart Diseases / etiology*
Heart Diseases / pathology*
Mice
Mice, Inbred DBA
Seizures / complications*