title: Chronic baroreceptor activation enhances survival in dogs with pacing-induced heart failure.
abstract: Much of the current pharmacological therapy for chronic heart failure targets neurohormonal activation. In spite of recent advances in drug therapy, the mortality rate for chronic heart failure remains high. Activation of the carotid baroreceptor (BR) reduces sympathetic outflow and augments vagal tone. We investigated the effect of chronic activation of the carotid BR on hemodynamic and neurohormonal parameters and on mortality in dogs with chronic heart failure. Fifteen dogs were instrumented to record hemodynamics. Electrodes were applied around the carotid sinuses to allow for activation of the BR. After 2 weeks of pacing (250 bpm), electrical carotid BR activation was initiated in 7 dogs and continued for the remainder of the study. The start of BR activation was used as a time reference point for the remaining 8 control dogs that did not receive BR activation. Survival was significantly greater for dogs undergoing carotid BR activation compared with control dogs (68.1+/-7.4 versus 37.3+/-3.2 days, respectively; P<0.01), although arterial pressure, resting heart rate, and left ventricular pressure were not different over time in BR-activated versus control dogs. Plasma norepinephrine was lower in dogs receiving BR activation therapy 31 days after the start of BR activation (401.9+/-151.5 versus 1121.9+/-389.1 pg/mL in dogs not receiving activation therapy; P<0.05). Plasma angiotensin II increased less in dogs receiving activation therapy (plasma angiotensin II increased by 157.4+/-58.6 pg/mL in control dogs versus 10.1+/-14.0 pg/mL in dogs receiving activation therapy; P<0.02). We conclude that chronic activation of the carotid BR improves survival and suppresses neurohormonal activation in chronic heart failure.
authors.affiliation: Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, 985850 Nebraska Medical Center, Omaha, NE 68198-5850, USA. izucker@unmc.edu
authors.forename: Irving H
authors.initials: IH
authors.lastname: Zucker
authors.forename: Johnnie F
authors.initials: JF
authors.lastname: Hackley
authors.forename: Kurtis G
authors.initials: KG
authors.lastname: Cornish
authors.forename: Bradley A
authors.initials: BA
authors.lastname: Hiser
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Anderson
authors.forename: Robert
authors.initials: R
authors.lastname: Kieval
authors.forename: Eric D
authors.initials: ED
authors.lastname: Irwin
authors.forename: David J
authors.initials: DJ
authors.lastname: Serdar
authors.forename: Jacob D
authors.initials: JD
authors.lastname: Peuler
authors.forename: Martin A
authors.initials: MA
authors.lastname: Rossing
mesh_terms: D000804:Angiotensin II / Q000097:blood; D000818:Animals; D001794:Blood Pressure; D002304:Cardiac Pacing, Artificial / Q000009:adverse effects; D002346:Carotid Sinus / Q000503:physiopathology*; D002908:Chronic Disease; D004285:Dogs; D004452:Echocardiography; D004599:Electric Stimulation Therapy / Q000379:methods*; D004562:Electrocardiography; D004567:Electrodes, Implanted; D006333:Heart Failure / Q000209:etiology / Q000503:physiopathology* / Q000628:therapy*; D006339:Heart Rate; D008297:Male; D009638:Norepinephrine / Q000097:blood; D011311:Pressoreceptors / Q000503:physiopathology*; D013318:Stroke Volume; D016019:Survival Analysis
chemical_list: D000804:Angiotensin II; D009638:Norepinephrine