title: Carotid chemoreceptor ablation improves survival in heart failure: rescuing autonomic control of cardiorespiratory function.
abstract: OBJECTIVE
  This study sought to investigate whether selective ablation of the carotid body (CB) chemoreceptors improves cardiorespiratory control and survival during heart failure.
  
  
  BACKGROUND
  Chronic heart failure (CHF) is a recognized health problem worldwide, and novel treatments are needed to better improve life quality and decrease mortality. Enhanced carotid chemoreflex drive from the CB is thought to contribute significantly to autonomic dysfunction, abnormal breathing patterns, and increased mortality in heart failure.
  
  
  METHODS
  Chronic heart failure was induced by coronary ligation in rats. Selective CB denervation was performed to remove carotid chemoreflex drive in the CHF state (16 weeks post-myocardial infarction). Indexes of autonomic and respiratory function were assessed in CB intact and CB denervated animals. CB denervation at 2 weeks post-myocardial infarction was performed to evaluate whether early targeted CB ablation decreases the progression of left ventricular dysfunction, cardiac remodeling, and arrhythmic episodes and improves survival.
  
  
  RESULTS
  The CHF rats developed increased CB chemoreflex drive and chronic central pre-sympathetic neuronal activation, increased indexes of elevated sympathetic outflow, increased breathing variability and apnea incidence, and desensitization of the baroreflex. Selective CB ablation reduced the central pre-sympathetic neuronal activation by 40%, normalized indexes of sympathetic outflow and baroreflex sensitivity, and reduced the incidence of apneas in CHF animals from 16.8 ± 1.8 events/h to 8.0 ± 1.4 events/h. Remarkably, when CB ablation was performed early, cardiac remodeling, deterioration of left ventricle ejection fraction, and cardiac arrhythmias were reduced. Most importantly, the rats that underwent early CB ablation exhibited an 85% survival rate compared with 45% survival in CHF rats without the intervention.
  
  
  CONCLUSIONS
  Carotid chemoreceptors play a seminal role in the pathogenesis of heart failure, and their targeted ablation might be of therapeutic value to reduce cardiorespiratory dysfunction and improve survival during CHF.
authors.affiliation: Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, Nebraska.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Del Rio
authors.affiliation: Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, Nebraska.
authors.forename: Noah J
authors.initials: NJ
authors.lastname: Marcus
authors.affiliation: Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, Nebraska. Electronic address: hschultz@unmc.edu.
authors.forename: Harold D
authors.initials: HD
authors.lastname: Schultz
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D002344:Carotid Body / Q000502:physiology*; D017115:Catheter Ablation / Q000379:methods; D002628:Chemoreceptor Cells / Q000502:physiology*; D006333:Heart Failure / Q000401:mortality / Q000503:physiopathology* / Q000601:surgery; D006339:Heart Rate / Q000502:physiology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015656:Respiratory Mechanics / Q000502:physiology*; D015996:Survival Rate / Q000639:trends
keywords: CAL; CB; CBD; CHF; EF; Fos-related antigen 1; Fra-1; HRV; IVS; LV; RVLM; autonomic function; breathing disorders; carotid body; carotid body denervation; chronic heart failure; coronary artery ligation; eCBD; early carotid body denervation; ejection fraction; heart failure; heart rate variability; interventricular septum; left ventricle/ventricular; mortality; rostral ventrolateral medulla