title: Chronic electrical stimulation of the carotid sinus baroreflex improves left ventricular function and promotes reversal of ventricular remodeling in dogs with advanced heart failure.
abstract: BACKGROUND
  Autonomic abnormalities exist in heart failure and contribute to disease progression. Activation of the carotid sinus baroreflex (CSB) has been shown to reduce sympathetic outflow and augment parasympathetic vagal tone. This study tested the hypothesis that long-term electric activation of the CSB improves left ventricular (LV) function and attenuates progressive LV remodeling in dogs with advanced chronic heart failure.
  
  
  RESULTS
  Studies were performed in 14 dogs with coronary microembolization-induced heart failure (LV ejection fraction ≈25%). Eight dogs were chronically instrumented for bilateral CSB activation using the Rheos System (CVRx Inc, Minneapolis, Minn) and 6 were not and served as controls. All dogs were followed for 3 months, and none received other background therapy. During follow-up, treatment with CSB increased LV ejection fraction 4.0±2.4% compared with a reduction in control dogs of −2.8±1.0% (P<0.05). Similarly, treatment with CSB decreased LV end-systolic volume -2.5±2.7 mL compared with an increase in control dogs of 6.7±2.9 mL (P<0.05). Compared with control, CSB activation significantly decreased LV end-diastolic pressure and circulating plasma norepinephrine, normalized expression of cardiac β(1)-adrenergic receptors, β-adrenergic receptor kinase, and nitric oxide synthase and reduced interstitial fibrosis and cardiomyocyte hypertrophy.
  
  
  CONCLUSIONS
  In dogs with advanced heart failure, CSB activation improves global LV function and partially reverses LV remodeling both globally and at cellular and molecular levels.
authors.affiliation: Department of Medicine, Division of Cardiovascular Medicine, Henry Ford Heart and Vascular Institute, 2799 W Grand Blvd., Detroit, MI 48202, USA. hsabbah1@hfhs.org
authors.forename: Hani N
authors.initials: HN
authors.lastname: Sabbah
authors.forename: Ramesh C
authors.initials: RC
authors.lastname: Gupta
authors.forename: Makoto
authors.initials: M
authors.lastname: Imai
authors.forename: Eric D
authors.initials: ED
authors.lastname: Irwin
authors.forename: Sharad
authors.initials: S
authors.lastname: Rastogi
authors.forename: Martin A
authors.initials: MA
authors.lastname: Rossing
authors.forename: Robert S
authors.initials: RS
authors.lastname: Kieval
mesh_terms: D000818:Animals; D017704:Baroreflex / Q000502:physiology*; D002346:Carotid Sinus / Q000503:physiopathology*; D004195:Disease Models, Animal; D018450:Disease Progression; D004285:Dogs; D004558:Electric Stimulation; D004562:Electrocardiography; D006333:Heart Failure / Q000378:metabolism / Q000503:physiopathology*; D006352:Heart Ventricles / Q000503:physiopathology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009638:Norepinephrine / Q000097:blood; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013318:Stroke Volume / Q000502:physiology; D020257:Ventricular Remodeling / Q000502:physiology*
chemical_list: D011943:Receptors, Adrenergic, beta; D019001:Nitric Oxide Synthase; D009638:Norepinephrine