IBCN   20355
INSTITUTO DE BIOLOGIA CELULAR Y NEUROCIENCIA "PROFESOR EDUARDO DE ROBERTIS"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Status Epilepticus induces P-glycoprotein overexpression in cardiomyocytes, heart dysfunction and high ratio of sudden death in rats.
Autor/es:
GELPI R; ZUBILLAGA M; BUCHHOLZ B; RAMOS AJ; MEN P; SALGUEIRO J; LAZAROWSKI A; MERELLI A; CANELLAS C; AUZMENDI JA
Lugar:
Buenos Aires
Reunión:
Congreso; 2° Reunión Conjunta de Biociencias; 2017
Resumen:
Sudden Unexpected Death in Epilepsy (SUDEP) is the most common cause of death after status epilepticus (SE). Refractory epilepsy was associated with P-glycoprotein (P-gp) brain overexpression and high risk of SUDEP by acute fatal heart failure. We have described brain/heart P-gp overexpression related with fatal-SE after repetitive penthylenetetrazole-induced seizures. Clinally, the loss of the 99mTc-SESTAMIBI retention is used as an in-vivo biomarker of hypoxic/ischemia (H/I) heart failure. After SE, loss of 99mTc-SESTAMIBI heart retention could be a risk factor marker for fatal heart failure. We induce SE on Wistar rats (300g; n=30) by lithium chloride (127 mg/kg;i.p.) plus pilocarpine (30 mg/kg;i.p.) 20hr later, and diazepam (20 mg/kg,i.p.) to stop SE after 20 m. We took three experimental groups with n=10 rats. In the first two groups, SE was induced once a week by four weeks. First group was used to evaluate P-gp and HIF-1 heart expression by immunohistochemistry after each SE. Second group was used to evaluate 99mTc-SESTAMIBI heart retention. After 72 h of SE, 99mTc-SESTAMIBI (37MBq-i.v) was administrated and static images of whole heart were acquired using a Gamma Camera for little animals. In the remaining group, SE was induced once. Heart rhythm and ECG registers were obtained 72 h after SE. We found an increased expression of P-gp and HIF-1 in cardiomyocytes, 50% reduced 99mTc-SESTAMIBI heart retention and increased mortality of the epileptic rats. Additionally ECG analysis showed both a decreased heart rate and extended QT time. We concluded that SE might act as H/I heart inducer with simultaneous overexpression of HIF-1 and P-gp in cardiomyocytes, severe loss of 99mTc-SESTAMIBI heart retentions and altered cardiac rhythms, associated with increased mortality. Under these conditions, new stress will start acute heart failure that could to lead in death, depending on severity of stress. These results could help to explain the mechanisms underlying in SUDEP.