Diaphragmatic Pacing to Prevent Seizure-Induced Respiratory Arrest in Mice
Abstract number :
2.42
Submission category :
3. Neurophysiology / 3F. Animal Studies
Year :
2022
Submission ID :
2233016
Source :
www.aesnet.org
Presentation date :
12/4/2022 12:00:00 PM
Published date :
Nov 22, 2022, 05:29 AM
Authors :
Benton Purnell, PhD – Robert Wood Johnson Medical School, Rutgers University; Alexander Braun, B.S. – Research Assistant, Neurosurgery, Rutgers University; Denise Fedele, PhD – Lab Manager, Neurosurgery, Rutgers University; Madhuvika Murugan, PhD – Senior Research Associate, Neurosurgery, Rutgers University; Detlev Boison, PhD – Principal Investigator, Neurosurgery, Rutgers University
This is a Late Breaking abstract
Rationale: Sudden unexpected death in epilepsy (SUDEP) is the leading cause of epilepsy related mortality. There are no known methods for reliably preventing SUDEP in patients with refractory epilepsy. The exact mechanistic underpinnings of SUDEP are unclear; however, evidence from epilepsy patients and animal models indicate that seizure-induced respiratory arrest is a critical contributor. Data from SUDEP and near-SUDEP events occurring in epilepsy monitoring units suggest that death may be prevented if artificial ventilation is rapidly initiated following the seizure. Diaphragmatic pacing is a surgical treatment strategy developed in the context of spinal cord injury which provides ventilatory support in instances where the patients own breathing would be insufficient or non-existent. In diaphragmatic pacing, rhythmic contractions of the diaphragm are elicited by electrical stimulation of the phrenic nerve or the diaphragm itself. These rhythmic contractions of the diaphragm cause air to be drawn into the lungs thereby providing artificial ventilation. We hypothesized that seizure-induced respiratory arrest and death in a mouse model could be prevented with diaphragmatic pacing.
Methods: Our approach was to induce respiratory arrest using maximal electroshock seizures in adult, male, C57BL6/J mice outfitted with EEG and diaphragmatic electrodes (n = 8 mice). In the experimental group, the diaphragm was stimulated to exogenously induce breathing. In the control group, no stimulation was applied. Breathing and cortical electrographic activity were monitored using whole body plethysmography and EEG, respectively.
Results: A majority of the animals that did not receive the diaphragmatic pacing intervention died of seizure-induced respiratory arrest. Conversely, none of the animals that received the diaphragmatic pacing intervention died. Diaphragmatic pacing improved postictal respiratory outcomes (two-way ANOVA, p < 0.001) and reduced the likelyhood of seizure-induced death (Fisher’s exact test, p = 0.026). Unexpectedly, diaphragmatic pacing did not instantly restore breathing during the postictal period, potentially indicating peripheral airway occlusion by laryngospasm. All diaphragmatically paced animals breathed at some point during the pacing stimulation. Two animals took their first breath prior to the onset of pacing and some animals had significant apneas after the pacing stimulation.
Neurophysiology