Carotid Body Stimulation to Prevent Sudden Death from Seizure
Abstract number :
2.052
Submission category :
3. Neurophysiology / 3F. Animal Studies
Year :
2021
Submission ID :
1825965
Source :
www.aesnet.org
Presentation date :
12/5/2021 12:00:00 PM
Published date :
Nov 22, 2021, 06:51 AM
Authors :
Ethan Biggs, BS - Purdue University; Ryan Budde - Purdue University; John Jefferys, PhD - Oxford University; Pedro Irazoqui, PhD - Purdue University
Rationale: Recent animal work has demonstrated that oxygen conserving reflexes may be significantly involved in sudden death mechanisms during seizure. In our previous work we have demonstrated that the mammalian diving reflex (MDR) and laryngeal chemoreflex (LCR) cause sudden death in two acute kainic acid seizure models in rats, but never in controls. Physiological data suggest that these deaths are similar to the cardiorespiratory collapse data available for cases of human Sudden Unexpected Death in Epilepsy (SUDEP).
Our previous data suggests death is caused by fatal MDR hyperactivation / improper inactivation. Available clinical and physiological data indicates that the carotid body is primarily responsible for ending the MDR and initiating respiration. Stimulation, denervation, or electroceutical modulation of the carotid body, the carotid sinus nerve, or the glossopharyngeal nerve may reasonably modify the MDR response during seizure, possibly even preventing deaths.
Methods: We anesthetized Long Evans rats with urethane (1.4 g/kg). We exposed the left carotid body and hooked microwire electrodes around the carotid sinus nerve. We applied constant-current, alternating phase square pulses of 1 ms pulse width, 7.5 Hz repeat frequency, and amplitude 0.3 – 5 mA. We obtained preictal recruitment curves and induced seizures with kainic acid (i.p. or intrahippocampal, 10 mg/kg or 6 µg, respectively). After seizures developed, we simultaneously induced the MDR and applied electrical stimulation to the carotid body. We repeated trials up to 12 times per animal.
Results: Carotid body stimulation significantly reduces mortality from ictal MDR (1/3 vs 10/10). Stimulation thresholds required to stimulate observable, repeatable physiological changes increase during seizure in excess of 10x their pre-ictal levels, indicating decreased brainstem sensitivity to peripheral chemoreceptor input.
Conclusions: Intervention at the carotid body or its afferents may be a clinically relevant electroceutical targets to prevent SUDEP in humans.
Funding: Please list any funding that was received in support of this abstract.: NIH OD023847.
Neurophysiology