The Effect of Antiseizure Medications and Cardioprotective Drugs on Cardiac Remodelling in a Post-status Epilepticus Rat Model of Temporal Lobe Epilepsy
Abstract number :
1.139
Submission category :
2. Translational Research / 2D. Models
Year :
2022
Submission ID :
2204593
Source :
www.aesnet.org
Presentation date :
12/3/2022 12:00:00 PM
Published date :
Nov 22, 2022, 05:25 AM
Authors :
Zining Liu, MSc, BSc – Monash University; Emma Braine, BSc – Monash University; bing Wang, PhD, MSc, BSc – Baker Heart and Diabetes Institute; piero Perucca, MD, PhD, FRACP – Monash University; shobi Sivathamboo, PhD – Monash University; Nigel Jones, PhD – Monash University; Terence O'Brien, MB, BS, MD, FRACP, FRCPE, FAHMS, FAES – Monash University; Pablo Casillas-Espinosa, MD, PhD – Monash University
This abstract is a recipient of the Suzanne and Peter Berry International Travel Award
This abstract has been invited to present during the Translational Research platform session
Rationale: A building body of clinical and experimental evidence indicates an increased risk of cardiac abnormalities in patients with chronic epilepsy, which may contribute towards increased morbidity and mortality in this population. This study aims to investigate functional and structural cardiac abnormalities in a rat model of chronic mesial temporal lobe epilepsy (TLE), and to investigate whether administration of the antiseizure medication levetiracetam (LEV), the cardioprotective drugs atenolol (B-blocker) or VCP979 (MAP kinase antagonist) could alleviate the changes in cardiac structure and function.
Methods: Kainic acid (KA) was used to induce status epilepticus (SE) and subsequent chronic epilepsy in male Wistar rats (n=32). LEV (200 mg/kg/day, n=9), atenolol (5 mg/kg/day, n=9), VCP979 (7 mg/kg/day, n=6) and vehicle (n=8) were administered through osmotic pump from day 0 post-SE to 4-12 weeks post-SE. Sham (n=12) rats were handled the same way but did not receive KA. EEG/ECG recordings were performed continuously for 2 weeks from 10 weeks post-KA SE to assess the chronic seizure frequency. Heart tissue was collected at 12 weeks post-SE and cardiac fibrosis was determined by PicroSirius Red staining of collagen. Statistical analysis was performed using student’s t-test, one-way ANOVA and the Kruskal-Wallis test.
Results: Animals in the post-SE groups experienced 0.4-14.2 seizures per day. We found no difference in seizure frequency among the post-SE groups receiving different treatments at the chronic timepoint (p=0.114). Compared to the sham control group, the degree of cardiac fibrosis was significantly higher in the vehicle-treated group and atenolol-treated group (4.51 ± 2.54 and 5.83 ± 3.00 vs. 2.13 ± 0.52 %, p=0.013 and p=0.002, respectively). There was a trend for increased cardiac fibrosis in the LEV treated group (4.58 ± 3.18, p=0.052) compared to shams. Notably, there was no difference in the VCP979 treated compared to the shams (2.78 ± 0.97, p >0.999) (Figure 1). There was a positive correlation between cardiac fibrosis level and seizure frequency in the vehicle-treated group (p=0.045, r2=0.516).
Conclusions: Our findings indicates that chronic epilepsy was associated with increased cardiac fibrosis. While the mechanisms underlying the cardiac fibrosis and potential cardiac dysfunction remains to be determined, we found that the novel anti-fibrotic and anti-inflammatory agent VCP979 may help prevent the development of myocardial fibrosis in chronic epilepsy, but a larger number of subjects and further investigation are required to confirm this hypothesis.
Funding: NHMRC Investigator Grant # APP1176426
Translational Research