Simultaneous cardiac and respiratory inhibition during seizure precedes death in the DBA/1 audiogenic mouse model of SUDEP

Autor: Diana L. Kunze, Tianen Yang, Carl L. Faingold, William P. Schilling, Morgan K McGrath, Patricia A. Glazebrook
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Critical Care and Emergency Medicine
Physiology
Respiratory arrest
Cardiovascular Physiology
Methylatropine
Tonic (physiology)
chemistry.chemical_compound
Mice
Electrocardiography
0302 clinical medicine
Heart Rate
Medicine and Health Sciences
Medicine
Respiratory system
Sudden Unexpected Death in Epilepsy
Lung
Multidisciplinary
Chemical Reactions
Heart
Animal Models
Respiratory Function Tests
Plethysmography
Chemistry
Bioassays and Physiological Analysis
Experimental Organism Systems
Neurology
Mice
Inbred DBA
Heart Function Tests
Physical Sciences
Cardiology
medicine.symptom
Research Article
Cardiac function curve
medicine.medical_specialty
Resuscitation
Science
Mouse Models
Research and Analysis Methods
Methylation
03 medical and health sciences
Model Organisms
Seizures
Internal medicine
Heart rate
Bradycardia
Animals
Humans
Asystole
Epilepsy
business.industry
Clonic Seizures
Electrophysiological Techniques
Biology and Life Sciences
Epileptic Seizures
medicine.disease
Disease Models
Animal
030104 developmental biology
chemistry
Control of respiration
Animal Studies
Cardiac Electrophysiology
business
030217 neurology & neurosurgery
Biomarkers
Zdroj: PLoS ONE, Vol 14, Iss 10, p e0223468 (2019)
PLoS ONE
ISSN: 1932-6203
Popis: This study was designed to evaluate cardiac and respiratory dysfunction in a mouse model of sudden unexpected death in epilepsy i.e., SUDEP. We simultaneously monitored respiration via plethysmography and the electrocardiogram via telemetry before, during, and after an audiogenic seizure. DBA/1 mice responded to an acoustic stimulus with one or two cycles of circling and jumping before entering a clonic/tonic seizure. This was followed by death unless the mice were resuscitated by mechanical ventilation using room air. During the initial clonic phase, respiration declined and cardiac rhythm is slowed. By the tonic phase, respiration had ceased, atrial P-waves were absent or dissociated from the QRS complex, and heart rate had decreased from 771±11 to 252±16 bpm. Heart rate further deteriorated terminating in asystole unless the mice were resuscitated at the end of the tonic phase which resulted in abrupt recovery of P-waves and a return to normal sinus rhythm, associated with gasping. Interestingly, P-waves were preserved in the mice treated with methylatropine during the pre-ictal period (to block parasympathetic stimulation) and heart rate remained unchanged through the end of the tonic phase (765±8 vs. 748±21 bpm), but as in control, methylatropine treated mice died from respiratory arrest. These results demonstrate that a clonic/tonic seizure in the DBA/1 mouse results in abrupt and simultaneous respiratory and cardiac depression. Although death clearly results from respiratory arrest, our results suggest that seizure activates two central nervous system pathways in this model-one inhibits respiratory drive, whereas the other inhibits cardiac function via vagal efferents. The abrupt and simultaneous recovery of both respiration and cardiac function with mechanical ventilation within an early post-ictal timeframe shows that the vagal discharge can be rapidly terminated. Understanding the central mechanism associated with the abrupt cardiorespiratory dysfunction and equally abrupt recovery may provide clues for therapeutic targets for SUDEP.
Databáze: OpenAIRE
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