title: Temporal Development of Autonomic Dysfunction in Heart Failure: Effects of Age in an Ovine Rapid-pacing Model.
abstract: Heart failure (HF) is predominantly a disease of older adults and characterized by extensive sympatho-vagal imbalance leading to impaired reflex control of heart rate (HR). However, whether aging influences the development or extent of the autonomic imbalance in HF remains unclear. To address this, we used an ovine model of aging with tachypacing-induced HF to determine whether aging affects the chronotropic and inotropic responses to autonomic stimulation and reduction in heart rate variability (HRV) in HF. We find that aging is associated with increased cardiac dimensions and reduced contractility before the onset of tachypacing, and these differences persist in HF. Additionally, the chronotropic response to β-adrenergic stimulation was markedly attenuated in HF, and this occurred more rapidly in aged animals. By measuring HR during sequential autonomic blockade, our data are consistent with a reduced parasympathetic control of resting HR in aging, with young HF animals having an attenuated sympathetic influence on HR. Time-domain analyses of HR show a reduction in HRV in both young and aged failing animals, although HRV is lowest in aged HF. In conclusion, aging is associated with altered autonomic control and β-adrenergic responsiveness of HR, and these are exacerbated with the development of HF.
authors.affiliation: Unit of Cardiac Physiology, Manchester Academic Health Sciences Centre.
authors.forename: Margaux A
authors.initials: MA
authors.lastname: Horn
authors.affiliation: Unit of Cardiac Physiology, Manchester Academic Health Sciences Centre.
authors.forename: Elizabeth F
authors.initials: EF
authors.lastname: Bode
authors.affiliation: Unit of Cardiac Physiology, Manchester Academic Health Sciences Centre.
authors.forename: Samantha J
authors.initials: SJ
authors.lastname: Borland
authors.affiliation: Unit of Cardiac Physiology, Manchester Academic Health Sciences Centre.
authors.forename: Graeme J
authors.initials: GJ
authors.lastname: Kirkwood
authors.affiliation: Unit of Cardiac Physiology, Manchester Academic Health Sciences Centre.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Briston
authors.affiliation: Unit of Cardiac Physiology, Manchester Academic Health Sciences Centre.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Richards
authors.affiliation: Unit of Cardiac Physiology, Manchester Academic Health Sciences Centre.
authors.forename: Katharine M
authors.initials: KM
authors.lastname: Dibb
authors.affiliation: Unit of Cardiac Physiology, Manchester Academic Health Sciences Centre. Andrew.W.Trafford@manchester.ac.uk.
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Trafford
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000367:Age Factors; D000818:Animals; D001341:Autonomic Nervous System / Q000503:physiopathology*; D015415:Biomarkers / Q000097:blood; D002304:Cardiac Pacing, Artificial; D004195:Disease Models, Animal; D004280:Dobutamine / Q000494:pharmacology; D004452:Echocardiography; D004562:Electrocardiography; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006333:Heart Failure / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006439:Hemodynamics; D009638:Norepinephrine / Q000097:blood; D034561:Sheep, Domestic; D013997:Time Factors
chemical_list: D000319:Adrenergic beta-Antagonists; D015415:Biomarkers; D004280:Dobutamine; D000109:Acetylcholine; D009638:Norepinephrine
keywords: Age-related pathology; Animal model; Cardiovascular disease