Chronic low-level vagus nerve stimulation improves long-term survival in salt-sensitive hypertensive rats

Elizabeth M. Annoni, Dusty Van Helden, Yugene Guo, Brett Levac, Imad Libbus, Bruce H. KenKnight, John W Osborn Jr, Alena Talkachova

Research output: Contribution to journalArticle

Abstract

Chronic hypertension (HTN) affects more than 1 billion people worldwide, and is associated with an increased risk of cardiovascular disease. Despite decades of promising research, effective treatment of HTN remains challenging. This work investigates vagus nerve stimulation (VNS) as a novel, device-based therapy for HTN treatment, and specifically evaluates its effects on long-term survival and HTN-associated adverse effects. HTN was induced in Dahl salt-sensitive rats using a high-salt diet, and the rats were randomly divided into two groups: VNS (n = 9) and Sham (n = 8), which were implanted with functional or non-functional VNS stimulators, respectively. Acute and chronic effects of VNS therapy were evaluated through continuous monitoring of blood pressure (BP) and ECG via telemetry devices. Autonomic tone was quantified using heart rate (HR), HR variability (HRV) and baroreflex sensitivity (BRS) analysis. Structural cardiac changes were quantified through gross morphology and histology studies. VNS significantly improved the long-term survival of hypertensive rats, increasing median event-free survival by 78% in comparison to Sham rats. Acutely, VNS improved autonomic balance by significantly increasing HRV during stimulation, which may lead to beneficial chronic effects of VNS therapy. Chronic VNS therapy slowed the progression of HTN through an attenuation of SBP and by preserving HRV. Finally, VNS significantly altered cardiac structure, increasing heart weight, but did not alter the amount of fibrosis in the hypertensive hearts. These results suggest that VNS has the potential to improve outcomes in subjects with severe HTN.

Original languageEnglish (US)
Article number25
JournalFrontiers in Physiology
Volume10
Issue numberJAN
DOIs
StatePublished - Jan 1 2019

Fingerprint

Vagus Nerve Stimulation
Salts
Hypertension
Therapeutics
Heart Rate
Inbred Dahl Rats
Equipment and Supplies
Telemetry
Baroreflex
Disease-Free Survival
Histology
Electrocardiography
Fibrosis
Cardiovascular Diseases
Diet
Blood Pressure

Keywords

  • Autonomic
  • Heart
  • Hypertension
  • Rat
  • Survival
  • Vagus nerve stimulation

PubMed: MeSH publication types

  • Journal Article

Cite this

Chronic low-level vagus nerve stimulation improves long-term survival in salt-sensitive hypertensive rats. / Annoni, Elizabeth M.; Van Helden, Dusty; Guo, Yugene; Levac, Brett; Libbus, Imad; KenKnight, Bruce H.; Osborn Jr, John W; Talkachova, Alena.

In: Frontiers in Physiology, Vol. 10, No. JAN, 25, 01.01.2019.

Research output: Contribution to journalArticle

Annoni, Elizabeth M. ; Van Helden, Dusty ; Guo, Yugene ; Levac, Brett ; Libbus, Imad ; KenKnight, Bruce H. ; Osborn Jr, John W ; Talkachova, Alena. / Chronic low-level vagus nerve stimulation improves long-term survival in salt-sensitive hypertensive rats. In: Frontiers in Physiology. 2019 ; Vol. 10, No. JAN.
@article{848cc06a578b4b0188be29b343b4949d,
title = "Chronic low-level vagus nerve stimulation improves long-term survival in salt-sensitive hypertensive rats",
abstract = "Chronic hypertension (HTN) affects more than 1 billion people worldwide, and is associated with an increased risk of cardiovascular disease. Despite decades of promising research, effective treatment of HTN remains challenging. This work investigates vagus nerve stimulation (VNS) as a novel, device-based therapy for HTN treatment, and specifically evaluates its effects on long-term survival and HTN-associated adverse effects. HTN was induced in Dahl salt-sensitive rats using a high-salt diet, and the rats were randomly divided into two groups: VNS (n = 9) and Sham (n = 8), which were implanted with functional or non-functional VNS stimulators, respectively. Acute and chronic effects of VNS therapy were evaluated through continuous monitoring of blood pressure (BP) and ECG via telemetry devices. Autonomic tone was quantified using heart rate (HR), HR variability (HRV) and baroreflex sensitivity (BRS) analysis. Structural cardiac changes were quantified through gross morphology and histology studies. VNS significantly improved the long-term survival of hypertensive rats, increasing median event-free survival by 78{\%} in comparison to Sham rats. Acutely, VNS improved autonomic balance by significantly increasing HRV during stimulation, which may lead to beneficial chronic effects of VNS therapy. Chronic VNS therapy slowed the progression of HTN through an attenuation of SBP and by preserving HRV. Finally, VNS significantly altered cardiac structure, increasing heart weight, but did not alter the amount of fibrosis in the hypertensive hearts. These results suggest that VNS has the potential to improve outcomes in subjects with severe HTN.",
keywords = "Autonomic, Heart, Hypertension, Rat, Survival, Vagus nerve stimulation",
author = "Annoni, {Elizabeth M.} and {Van Helden}, Dusty and Yugene Guo and Brett Levac and Imad Libbus and KenKnight, {Bruce H.} and {Osborn Jr}, {John W} and Alena Talkachova",
year = "2019",
month = "1",
day = "1",
doi = "10.3389/fphys.2019.00025",
language = "English (US)",
volume = "10",
journal = "Frontiers in Physiology",
issn = "1664-042X",
publisher = "Frontiers Research Foundation",
number = "JAN",

}

TY - JOUR

T1 - Chronic low-level vagus nerve stimulation improves long-term survival in salt-sensitive hypertensive rats

AU - Annoni, Elizabeth M.

AU - Van Helden, Dusty

AU - Guo, Yugene

AU - Levac, Brett

AU - Libbus, Imad

AU - KenKnight, Bruce H.

AU - Osborn Jr, John W

AU - Talkachova, Alena

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Chronic hypertension (HTN) affects more than 1 billion people worldwide, and is associated with an increased risk of cardiovascular disease. Despite decades of promising research, effective treatment of HTN remains challenging. This work investigates vagus nerve stimulation (VNS) as a novel, device-based therapy for HTN treatment, and specifically evaluates its effects on long-term survival and HTN-associated adverse effects. HTN was induced in Dahl salt-sensitive rats using a high-salt diet, and the rats were randomly divided into two groups: VNS (n = 9) and Sham (n = 8), which were implanted with functional or non-functional VNS stimulators, respectively. Acute and chronic effects of VNS therapy were evaluated through continuous monitoring of blood pressure (BP) and ECG via telemetry devices. Autonomic tone was quantified using heart rate (HR), HR variability (HRV) and baroreflex sensitivity (BRS) analysis. Structural cardiac changes were quantified through gross morphology and histology studies. VNS significantly improved the long-term survival of hypertensive rats, increasing median event-free survival by 78% in comparison to Sham rats. Acutely, VNS improved autonomic balance by significantly increasing HRV during stimulation, which may lead to beneficial chronic effects of VNS therapy. Chronic VNS therapy slowed the progression of HTN through an attenuation of SBP and by preserving HRV. Finally, VNS significantly altered cardiac structure, increasing heart weight, but did not alter the amount of fibrosis in the hypertensive hearts. These results suggest that VNS has the potential to improve outcomes in subjects with severe HTN.

AB - Chronic hypertension (HTN) affects more than 1 billion people worldwide, and is associated with an increased risk of cardiovascular disease. Despite decades of promising research, effective treatment of HTN remains challenging. This work investigates vagus nerve stimulation (VNS) as a novel, device-based therapy for HTN treatment, and specifically evaluates its effects on long-term survival and HTN-associated adverse effects. HTN was induced in Dahl salt-sensitive rats using a high-salt diet, and the rats were randomly divided into two groups: VNS (n = 9) and Sham (n = 8), which were implanted with functional or non-functional VNS stimulators, respectively. Acute and chronic effects of VNS therapy were evaluated through continuous monitoring of blood pressure (BP) and ECG via telemetry devices. Autonomic tone was quantified using heart rate (HR), HR variability (HRV) and baroreflex sensitivity (BRS) analysis. Structural cardiac changes were quantified through gross morphology and histology studies. VNS significantly improved the long-term survival of hypertensive rats, increasing median event-free survival by 78% in comparison to Sham rats. Acutely, VNS improved autonomic balance by significantly increasing HRV during stimulation, which may lead to beneficial chronic effects of VNS therapy. Chronic VNS therapy slowed the progression of HTN through an attenuation of SBP and by preserving HRV. Finally, VNS significantly altered cardiac structure, increasing heart weight, but did not alter the amount of fibrosis in the hypertensive hearts. These results suggest that VNS has the potential to improve outcomes in subjects with severe HTN.

KW - Autonomic

KW - Heart

KW - Hypertension

KW - Rat

KW - Survival

KW - Vagus nerve stimulation

UR - http://www.scopus.com/inward/record.url?scp=85065483007&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85065483007&partnerID=8YFLogxK

U2 - 10.3389/fphys.2019.00025

DO - 10.3389/fphys.2019.00025

M3 - Article

C2 - 30766489

AN - SCOPUS:85065483007

VL - 10

JO - Frontiers in Physiology

JF - Frontiers in Physiology

SN - 1664-042X

IS - JAN

M1 - 25

ER -