Authors :
Presenting Author: Aline Priscila Pansani, PhD – Universidade Federal de Goias
Diego Colugnati, PhD – Professor, Department of Physiological Sciences, Universidade Federal de Goias; Eduardo Bravo, PhD – Department of Neurology – University of Iowa; Cláudio Quintino, MSc – Department of Physiological Sciences – Universidade Federal de Goiás; Isabella Anania, Bsc – University of Iowa; Angel Kelley, BSc – University of Iowa; George Richerson, MD, PhD – Professor, Department of Neurology, University of Iowa
Rationale:
Sudden Unexpected Death in Epilepsy (SUDEP) affects 0.1% of individuals with epilepsy. Among the mechanisms related to SUDEP are respiratory alterations such as ictal apneas and reduction in central chemoreflex. However, it is still unknown how epilepsy can alter chemoreflex mechanisms in some individuals but not in others. Therefore, our aim was to evaluate the chemoreflex, through the ventilatory responses to hypercapnia and hypoxia (HCVR and HCVR, respectively) in chronic epilepsy. Additionally, we analyzed whether the HCVR and HVR responses were altered following a spontaneous generalized tonic-clonic seizure (GTCS), which is the main risk factor for SUDEP.
Methods:
For that, male Wistar rats were submitted to the pilocarpine model of epilepsy. After the status epilepticus, the rats were video monitored until the first spontaneous seizure occurred (start of chronic period). After 30 days, rats (interictal group, n=8) were placed in a whole-body plethysmography chamber for testing the HCVR (Baseline 0% CO
2 and 50% O
2 followed by 7% CO
2 and 50% O
2) and HVR (Baseline 0% CO
2 and 50% O
2, followed by 0% CO
2 and 10% O
2). When we observed a rat having a spontaneous seizure in the video-monitoring room, that rat was placed in the plethysmography chamber after the seizure ended (post-ictal group, n=7), and HCVR and HVR tests were run. In that group, the timing of the tests ranged from 10 to 60 minutes after the seizure ended. The control group consisted of rats not treated with pilocarpine, and age-matched with the epilepsy group (control group, n=8). The following variables were assessed: minute ventilation (VE), tidal volume (Vt), and respiratory frequency (fR) corrected by weight and in proportion of the change.
Results:
In the HCVR test, both the interictal and post-ictal epilepsy groups had reduced fR values at baseline and at 7% CO
2 compared to the control group. However, there was no significant difference in the proportion of fR increase among the groups. Conversely, in HVR test both the interictal and post-ictal epilepsy groups had lower baseline values of VE and fR, while the proportion of increase in VE, Vt, and fR was higher in the epilepsy groups compared to the control group. There was no difference in HCVR and HVR between the interictal and post-ictal groups.
Conclusions:
These findings suggest that chronic epilepsy induced by Pilocarpine leads to enhanced sensitivity to hypoxia, indicating hyperactivity of peripheral chemoreceptors. This response may suggest an adaptive mechanism aimed at maintaining adequate gas exchange during seizures.
Funding:
Fulbright Scholar Program