Avaliação das respostas cardiovasculares e eletroencefalográficas após crises epilépticas induzidas pelo abrasamento elétrico da amígdala em diferentes fases do ciclo sono-vigília de ratos

Abstract

Introduction: Cardiovascular alterations have been identified as the main cause of Sudden Unexpected Death in Epilepsy (SUDEP). There is an intimate relationship between epilepsy and sleep. Most cases of SUDEP occurs during sleep and the NREM sleep is a facilitator factor for the occurence of seizures. Aim: To evaluate cardiovascular and electroencephalographic responses of rats submitted to kindling model induced at diferente stages of sleep-wake cycle. Methods: The experimental protocol was approved by Ethics Commitee of the Universidade Federal de Goiás (CEUA-035/2015). Wistar rats (250-350 g) were separeted into 4 groups and seizures were induced according to sleep-wake cycle (Wake, NREM sleep and REM sleep) or no seizure (SHAM). We used the kindling model for induction of seizures. The animals was submitted to stereotactic surgery to implant electrodes in the right amygdala, for electrical stimulation, and in the cortex, for electroencephalographic record (EEGc). Electrodes for electromyographic (EMG) and electrocardiographic (ECG) recordings were also implanted. The detection of sleep phase was based on algorithms described by Louis et al. (2003). The electrical stimulus was induced one time per day and consisted in a biphasic wave during 2 seconds (60 Hz). The seizures evolution was analyzed according to Racine’s scale (E1: orofacial movements; E2: mastigatory movements and head clonus; E3: forelimb clonus; E4: rearing; E5: rearing and falling). Three E5 seizures was induced in each animal. We evaluated heart rate (HR), heart rate variability (HRV) arrhythmias and EEGc in vivo, cardiac function and vascular reactivity ex vivo. Results: The time fully kindling in NREM group was lower compared to Wake group. The NREM group presents postictal tachycardia in the early stages of process. The duration of postictal generalized electroencephalogram supression (PGES) is larger in REM group. The PGES in Wake group was accompanied by a decrease in HR compared to the final period of seizures. The muscle cell in aortic artery of Wake group had greater contraction capacity than the other groups, while the REM group had a higher endothelium-dependent relaxatio. Parameters such as after-discharge duration (AD), HR and HRV after kindling process, arrhythmias, bradycardia followed by tachycardia during the ictal period of E5 seizures and ex vivo cardiac funtion were similar in all groups. Conclusion: Our results suggest that kindling process per se was able to induce an increase in post-ictal HR in NREM group, an increase in PGES duration in REM group, and an impairment on vascular reactivity of NREM (higher contraction percentage) and REM (lower relaxation percentage) groups.