Threshold adjusted vagus nerve stimulation after asphyxial cardiac arrest results in neuroprotection and improved survival.

Cardiac arrest Ischemia-reperfusion injury Neuroprotection Vagus nerve stimulation

Journal

Bioelectronic medicine
ISSN: 2332-8886
Titre abrégé: Bioelectron Med
Pays: England
ID NLM: 101660849

Informations de publication

Date de publication:
20 Jul 2022
Historique:
received: 30 05 2022
accepted: 24 06 2022
entrez: 19 7 2022
pubmed: 20 7 2022
medline: 20 7 2022
Statut: epublish

Résumé

Vagus nerve stimulation (VNS) has shown therapeutic potential in a variety of different diseases with many ongoing clinical trials. The role of VNS in reducing ischemic injury in the brain requires further evaluation. Cardiac arrest (CA) causes global ischemia and leads to the injury of vital organs, especially the brain. In this study, we investigated the protective effects of customized threshold-adjusted VNS (tVNS) in a rat model of CA and resuscitation. Sprague-Dawley rats underwent 12 min asphyxia-CA followed by resuscitation. Rats were assigned to either post-resuscitation tVNS for 2 h or no-tVNS (control). tVNS was applied by electrode placement in the left cervical vagus nerve. To optimize a threshold, we used animal's heart rate and determined a 15-20% drop from baseline levels as the effective and physiological threshold for each animal. The primary endpoint was 72 h survival; secondary endpoints included neurological functional recovery, reduction in brain cellular injury (histopathology), cardiac and renal injury parameters (troponin I and creatinine levels, respectively). In comparison to the control group, tVNS significantly improved 72 h survival and brain functional recovery after 12 minutes of CA. The tVNS group demonstrated significantly reduced numbers of damaged neurons in the CA1 hippocampal region of the brain as compared to the control group. Similarly, the tVNS group showed decreased trend in plasma troponin I and creatinine levels as compared to the control group. Our findings suggest that using tVNS for 2 h after 12 minutes of CA attenuates ischemia neuronal cell death, heart and kidney damage, and improves 72 h survival with improved neurological recovery.

Sections du résumé

BACKGROUND BACKGROUND
Vagus nerve stimulation (VNS) has shown therapeutic potential in a variety of different diseases with many ongoing clinical trials. The role of VNS in reducing ischemic injury in the brain requires further evaluation. Cardiac arrest (CA) causes global ischemia and leads to the injury of vital organs, especially the brain. In this study, we investigated the protective effects of customized threshold-adjusted VNS (tVNS) in a rat model of CA and resuscitation.
METHODS METHODS
Sprague-Dawley rats underwent 12 min asphyxia-CA followed by resuscitation. Rats were assigned to either post-resuscitation tVNS for 2 h or no-tVNS (control). tVNS was applied by electrode placement in the left cervical vagus nerve. To optimize a threshold, we used animal's heart rate and determined a 15-20% drop from baseline levels as the effective and physiological threshold for each animal. The primary endpoint was 72 h survival; secondary endpoints included neurological functional recovery, reduction in brain cellular injury (histopathology), cardiac and renal injury parameters (troponin I and creatinine levels, respectively).
RESULTS RESULTS
In comparison to the control group, tVNS significantly improved 72 h survival and brain functional recovery after 12 minutes of CA. The tVNS group demonstrated significantly reduced numbers of damaged neurons in the CA1 hippocampal region of the brain as compared to the control group. Similarly, the tVNS group showed decreased trend in plasma troponin I and creatinine levels as compared to the control group.
CONCLUSIONS CONCLUSIONS
Our findings suggest that using tVNS for 2 h after 12 minutes of CA attenuates ischemia neuronal cell death, heart and kidney damage, and improves 72 h survival with improved neurological recovery.

Identifiants

pubmed: 35854394
doi: 10.1186/s42234-022-00092-0
pii: 10.1186/s42234-022-00092-0
pmc: PMC9297561
doi:

Types de publication

Journal Article

Langues

eng

Pagination

10

Subventions

Organisme : NIGMS NIH HHS
ID : R35 GM118182
Pays : United States

Informations de copyright

© 2022. The Author(s).

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Auteurs

Rishabh C Choudhary (RC)

Laboratory for Critical Care Physiology, Feinstein Institutes for Medical Research, Northwell Health, 350 Community Dr, Manhasset, NY, 11030, USA.
Institute of Bioelectronic Medicine, Feinstein Institutes for Medical Research, Manhasset, NY, USA.
Department of Emergency Medicine, Northwell Health, Manhasset, NY, USA.

Umair Ahmed (U)

Institute of Bioelectronic Medicine, Feinstein Institutes for Medical Research, Manhasset, NY, USA.

Muhammad Shoaib (M)

Laboratory for Critical Care Physiology, Feinstein Institutes for Medical Research, Northwell Health, 350 Community Dr, Manhasset, NY, 11030, USA.
Institute of Bioelectronic Medicine, Feinstein Institutes for Medical Research, Manhasset, NY, USA.
Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA.

Eric Alper (E)

Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA.

Abdul Rehman (A)

Laboratory for Critical Care Physiology, Feinstein Institutes for Medical Research, Northwell Health, 350 Community Dr, Manhasset, NY, 11030, USA.

Junhwan Kim (J)

Laboratory for Critical Care Physiology, Feinstein Institutes for Medical Research, Northwell Health, 350 Community Dr, Manhasset, NY, 11030, USA.
Institute of Bioelectronic Medicine, Feinstein Institutes for Medical Research, Manhasset, NY, USA.
Department of Emergency Medicine, Northwell Health, Manhasset, NY, USA.
Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA.

Koichiro Shinozaki (K)

Laboratory for Critical Care Physiology, Feinstein Institutes for Medical Research, Northwell Health, 350 Community Dr, Manhasset, NY, 11030, USA.
Department of Emergency Medicine, Northwell Health, Manhasset, NY, USA.
Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA.

Bruce T Volpe (BT)

Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA.
Center for Molecular Medicine, Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, USA.

Sangeeta Chavan (S)

Institute of Bioelectronic Medicine, Feinstein Institutes for Medical Research, Manhasset, NY, USA.

Stavros Zanos (S)

Institute of Bioelectronic Medicine, Feinstein Institutes for Medical Research, Manhasset, NY, USA.

Kevin J Tracey (KJ)

Institute of Bioelectronic Medicine, Feinstein Institutes for Medical Research, Manhasset, NY, USA.

Lance B Becker (LB)

Laboratory for Critical Care Physiology, Feinstein Institutes for Medical Research, Northwell Health, 350 Community Dr, Manhasset, NY, 11030, USA. lance.becker@northwell.edu.
Institute of Bioelectronic Medicine, Feinstein Institutes for Medical Research, Manhasset, NY, USA. lance.becker@northwell.edu.
Department of Emergency Medicine, Northwell Health, Manhasset, NY, USA. lance.becker@northwell.edu.

Classifications MeSH