Simvastatin treatment attenuates increased respiratory variability and apnea/hypopnea index in rats with chronic heart failure

Karla K V Haack, Noah J. Marcus, Rodrigo Del Rio, Irving H Zucker, Harold D Schultz

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Cheyne-Stokes respiration and cardiac arrhythmias are associated with increased morbidity and mortality in patients with chronic heart failure (CHF). Enhanced carotid body chemoreflex (CBC) sensitivity is associated with these abnormalities in CHF. Reduced carotid body (CB) nitric oxide and nitric oxide synthase (NOS) levels play an important role in the enhanced CBC. In other disease models, Simvastatin (statin) treatment increases endothelial NOS, in part, by increasing Krüppel-like Factor 2 expression. We hypothesized that statin treatment would ameliorate enhanced CBC sensitivity as well as increased respiratory variability, apnea/hypopnea index, and arrhythmia index, in a rodent model of CHF. Resting breathing pattern, cardiac rhythm, and the ventilatory and CB chemoreceptor afferent responses to hypoxia were assessed in rats with CHF induced by coronary ligation. CHF was associated with enhanced ventilatory and CB afferent responses to hypoxia as well as increased respiratory variability, apnea/hypopnea index, and arrhythmia index. Statin treatment prevented the increases in CBC sensitivity and the concomitant increases in respiratory variability, apnea/hypopnea index, and arrhythmia index. Krüppel-like Factor 2 and endothelial NOS protein were decreased in the CB and nucleus tractus solitarii of CHF animals, and statin treatment increased the expression of these proteins. Our findings demonstrate that the increased CBC sensitivity, respiratory instability, and cardiac arrhythmias observed in CHF are ameliorated by statin treatment and suggest that statins may be an effective treatment for Cheyne-Stokes respiration and arrhythmias in patient populations with high chemoreflex sensitivity.

Original languageEnglish (US)
Pages (from-to)1041-1049
Number of pages9
JournalHypertension
Volume63
Issue number5
DOIs
StatePublished - Jan 1 2014

Fingerprint

Carotid Body
Simvastatin
Apnea
Heart Failure
Cardiac Arrhythmias
Cheyne-Stokes Respiration
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Therapeutics
Nitric Oxide Synthase Type III
Solitary Nucleus
Nitric Oxide Synthase
Ligation
Rodentia
Nitric Oxide
Respiration
Proteins
Morbidity
Mortality

Keywords

  • Carotid body
  • Cheyne-Stokes Respiration
  • Simvastatin
  • Systolic heart failure

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Simvastatin treatment attenuates increased respiratory variability and apnea/hypopnea index in rats with chronic heart failure. / Haack, Karla K V; Marcus, Noah J.; Del Rio, Rodrigo; Zucker, Irving H; Schultz, Harold D.

In: Hypertension, Vol. 63, No. 5, 01.01.2014, p. 1041-1049.

Research output: Contribution to journalArticle

@article{f3eff122b1304d6db6f7f03cac6b2bb6,
title = "Simvastatin treatment attenuates increased respiratory variability and apnea/hypopnea index in rats with chronic heart failure",
abstract = "Cheyne-Stokes respiration and cardiac arrhythmias are associated with increased morbidity and mortality in patients with chronic heart failure (CHF). Enhanced carotid body chemoreflex (CBC) sensitivity is associated with these abnormalities in CHF. Reduced carotid body (CB) nitric oxide and nitric oxide synthase (NOS) levels play an important role in the enhanced CBC. In other disease models, Simvastatin (statin) treatment increases endothelial NOS, in part, by increasing Kr{\"u}ppel-like Factor 2 expression. We hypothesized that statin treatment would ameliorate enhanced CBC sensitivity as well as increased respiratory variability, apnea/hypopnea index, and arrhythmia index, in a rodent model of CHF. Resting breathing pattern, cardiac rhythm, and the ventilatory and CB chemoreceptor afferent responses to hypoxia were assessed in rats with CHF induced by coronary ligation. CHF was associated with enhanced ventilatory and CB afferent responses to hypoxia as well as increased respiratory variability, apnea/hypopnea index, and arrhythmia index. Statin treatment prevented the increases in CBC sensitivity and the concomitant increases in respiratory variability, apnea/hypopnea index, and arrhythmia index. Kr{\"u}ppel-like Factor 2 and endothelial NOS protein were decreased in the CB and nucleus tractus solitarii of CHF animals, and statin treatment increased the expression of these proteins. Our findings demonstrate that the increased CBC sensitivity, respiratory instability, and cardiac arrhythmias observed in CHF are ameliorated by statin treatment and suggest that statins may be an effective treatment for Cheyne-Stokes respiration and arrhythmias in patient populations with high chemoreflex sensitivity.",
keywords = "Carotid body, Cheyne-Stokes Respiration, Simvastatin, Systolic heart failure",
author = "Haack, {Karla K V} and Marcus, {Noah J.} and {Del Rio}, Rodrigo and Zucker, {Irving H} and Schultz, {Harold D}",
year = "2014",
month = "1",
day = "1",
doi = "10.1161/HYPERTENSIONAHA.113.02535",
language = "English (US)",
volume = "63",
pages = "1041--1049",
journal = "Hypertension",
issn = "0194-911X",
publisher = "Lippincott Williams and Wilkins",
number = "5",

}

TY - JOUR

T1 - Simvastatin treatment attenuates increased respiratory variability and apnea/hypopnea index in rats with chronic heart failure

AU - Haack, Karla K V

AU - Marcus, Noah J.

AU - Del Rio, Rodrigo

AU - Zucker, Irving H

AU - Schultz, Harold D

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Cheyne-Stokes respiration and cardiac arrhythmias are associated with increased morbidity and mortality in patients with chronic heart failure (CHF). Enhanced carotid body chemoreflex (CBC) sensitivity is associated with these abnormalities in CHF. Reduced carotid body (CB) nitric oxide and nitric oxide synthase (NOS) levels play an important role in the enhanced CBC. In other disease models, Simvastatin (statin) treatment increases endothelial NOS, in part, by increasing Krüppel-like Factor 2 expression. We hypothesized that statin treatment would ameliorate enhanced CBC sensitivity as well as increased respiratory variability, apnea/hypopnea index, and arrhythmia index, in a rodent model of CHF. Resting breathing pattern, cardiac rhythm, and the ventilatory and CB chemoreceptor afferent responses to hypoxia were assessed in rats with CHF induced by coronary ligation. CHF was associated with enhanced ventilatory and CB afferent responses to hypoxia as well as increased respiratory variability, apnea/hypopnea index, and arrhythmia index. Statin treatment prevented the increases in CBC sensitivity and the concomitant increases in respiratory variability, apnea/hypopnea index, and arrhythmia index. Krüppel-like Factor 2 and endothelial NOS protein were decreased in the CB and nucleus tractus solitarii of CHF animals, and statin treatment increased the expression of these proteins. Our findings demonstrate that the increased CBC sensitivity, respiratory instability, and cardiac arrhythmias observed in CHF are ameliorated by statin treatment and suggest that statins may be an effective treatment for Cheyne-Stokes respiration and arrhythmias in patient populations with high chemoreflex sensitivity.

AB - Cheyne-Stokes respiration and cardiac arrhythmias are associated with increased morbidity and mortality in patients with chronic heart failure (CHF). Enhanced carotid body chemoreflex (CBC) sensitivity is associated with these abnormalities in CHF. Reduced carotid body (CB) nitric oxide and nitric oxide synthase (NOS) levels play an important role in the enhanced CBC. In other disease models, Simvastatin (statin) treatment increases endothelial NOS, in part, by increasing Krüppel-like Factor 2 expression. We hypothesized that statin treatment would ameliorate enhanced CBC sensitivity as well as increased respiratory variability, apnea/hypopnea index, and arrhythmia index, in a rodent model of CHF. Resting breathing pattern, cardiac rhythm, and the ventilatory and CB chemoreceptor afferent responses to hypoxia were assessed in rats with CHF induced by coronary ligation. CHF was associated with enhanced ventilatory and CB afferent responses to hypoxia as well as increased respiratory variability, apnea/hypopnea index, and arrhythmia index. Statin treatment prevented the increases in CBC sensitivity and the concomitant increases in respiratory variability, apnea/hypopnea index, and arrhythmia index. Krüppel-like Factor 2 and endothelial NOS protein were decreased in the CB and nucleus tractus solitarii of CHF animals, and statin treatment increased the expression of these proteins. Our findings demonstrate that the increased CBC sensitivity, respiratory instability, and cardiac arrhythmias observed in CHF are ameliorated by statin treatment and suggest that statins may be an effective treatment for Cheyne-Stokes respiration and arrhythmias in patient populations with high chemoreflex sensitivity.

KW - Carotid body

KW - Cheyne-Stokes Respiration

KW - Simvastatin

KW - Systolic heart failure

UR - http://www.scopus.com/inward/record.url?scp=84902275098&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84902275098&partnerID=8YFLogxK

U2 - 10.1161/HYPERTENSIONAHA.113.02535

DO - 10.1161/HYPERTENSIONAHA.113.02535

M3 - Article

VL - 63

SP - 1041

EP - 1049

JO - Hypertension

JF - Hypertension

SN - 0194-911X

IS - 5

ER -