# Sequence of physiological events during oxygen conserving reflex activation leading to sudden death in epilepsy

> **NIH NIH R01** · PURDUE UNIVERSITY · 2021 · $58,329

## Abstract

Project Summary
Sudden unexpected death in epilepsy (SUDEP) is a fatal complication of epilepsy that kills approximately
4,000 Americans every year. SUDEP is difficult to study because, while common, it usually occurs unobserved.
The limited clinical data that exists suggests that SUDEP is a cardiorespiratory collapse that occurs directly
after a seizure. Cardiorespiratory function is largely modulated by the autonomic nervous system (ANS).
Sympathetic and parasympathetic autonomic nervous system pathways typically operate in opposition, so co-
activation is rare. In the Oxygen Conserving family of Reflexes (OCRs), both pathways co-activate to induce
breath-holding (apnea), lowered heart rate (bradycardia), and narrowing of peripheral blood vessels
(vasoconstriction). Apnea prevents aspiration. Bradycardia conserves oxygen. Vasoconstriction prioritizes
blood-carrying oxygen to essential organs (i.e. heart and brain). Seizure-induced autonomic disfunction,
coupled with an externally triggered OCR may lead to death in Sudden Unexpected Death in Epilepsy
(SUDEP). To elucidate the causal relationship between physiological parameters, OCRs, and sudden death,
we propose to measure a physiological baseline of various oxygen conserving reflexes in healthy, anesthetized
animals in Aim 1. This will establish a baseline for the temporal relationship between: cardiac, respiratory, and
neural physiological signals in healthy animals before, during, and after OCR. It will also provide an important
data set for subsequent exploration of causal relationships between those signals in both healthy and
autonomically compromised subjects. Implications extend beyond SUDEP. In Aim 2 will then identify changes
from the physiological baseline in various oxygen conserving reflexes for seizing animals. This will provide data
of the specific role of various models of epilepsy, on compromising the autonomic system in the context of
triggered OCR, and will show the unique sequence of events leading to sudden death in seizing animals. In
Aim 3 we shift from acute to chronic animal models. We will determine the importance of awake, freely-
behaving, chronic epilepsy on the physiological chain-of-events implicated in sudden death. We will do this
using previously developed by us implantable devices to monitor the complete range of physiological
parameters in chronic, freely-behaving male and female rats. Separating seizing and non-seizing, OCR vs no-
OCR, responses in the same freely-moving animal over time will provide an entirely new window into the role
of sympathetic and parasympathetic co-activation in normal and autonomic-compromised subjects.

## Key facts

- **NIH application ID:** 10097583
- **Project number:** 1R01NS119390-01
- **Recipient organization:** PURDUE UNIVERSITY
- **Principal Investigator:** Pedro Irazoqui
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $58,329
- **Award type:** 1
- **Project period:** 2020-12-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10097583

## Citation

> US National Institutes of Health, RePORTER application 10097583, Sequence of physiological events during oxygen conserving reflex activation leading to sudden death in epilepsy (1R01NS119390-01). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10097583. Licensed CC0.

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