Alterations in the autonomic control of heart rate and heart rate variability in an ovine model of heart failure

Horn, Margaux; Richards, Mark; Clarke, Jessica; Greensmith, David; Briston, Sarah; Hall, M; Eisner, David; Dibb, Katherine; Trafford, Andrew

Abstract

Heart failure (HF) is a clinical syndrome characterised by reduced contractility, ventricular dilatation and alterations to cellular, extracellular, neural and circulating factors. The aim of the present study was to develop a translationally useful model of heart failure and investigate the function of the autonomic nervous system with respect to control of heart rate and heart rate variability. Twelve adult sheep (18 months) were anaesthetised with isoflurane (1-3% in oxygen) and perioperative analgesia provided (meloxicam, 0.5 mg/kg). A single IS-1 bipolar pacing lead was implanted transvenously in to the right ventricular chamber and connected to a pacemaker (Kappa, Medtronic) located sub-cutaneously in the right lateral cervical region. Approximately 7 – 10 days post-surgery HF was induced by 4 weeks of rapid right ventricular pacing (RVP) at 3.5Hz. Continuous electrocardiogram (ECG) recordings were made on conscious animals using a five-lead orthogonal ECG. Signals were digitised at 1Khz onto PC (IOX, EMKA Technologies). Autonomic function was assessed prior to activation of RVP (control) and 15 -30 minutes after RVP was stopped when HF had developed (HF). Autonomic function was determined by intravenous administration of propanolol (0.5 mg/kg) and atropine (0.05mg/kg). The ECG RR interval, RR interval standard deviation (SD) and QT interval were measured using shape recognition algorhythms (ECG Auto, EMKA Technologies). Data are presented as mean ± SEM. Statistical significance differences were determined using the paired t-test. Before pacing commenced propanolol slowed heart rate (RR interval increasing from 575 ± 32ms to 815 ± 70ms, n=12, P<0.01). Full autonomic block after propranolol administration increased heart rate (RR interval, 489 ± 17ms, P=0.001). After 4 weeks RVP, propanolol again slowed heart rate, however there was a trend towards this response being smaller than prior to pacing (RR interval, 815 ± 70ms vs. 674 ± 21ms, P=0.07). In HF full autonomic block failed to change heart rate after propanolol administration (RR interval, 669 ± 24ms, P=0.787). Assessment of HR variability as measured from the standard deviation of the RR interval showed that HR variability was increased by propranolol to a much greater extent before pacing commenced (69 ± 16 vs. 34 ± 6, P<0.05). QT interval, was also increased by 17% in paced animals compared to pre-pacing (P<0.001). These data suggest that perturbations to both sympathetic and parasympathetic control of heart rate occur in HF. All procedures accord to The UK Animals (Scientific Procedures) Act, 1986.

• Presentation Conference Type: Conference Abstract
• Conference Name: Physiology 2010
• Start Date: Jul 5, 2010
• End Date: Jul 8, 2010
• Acceptance Date: Jul 5, 2010
• Online Publication Date: Jul 5, 2010
• Publication Date: Jul 5, 2010
• Deposit Date: Jun 24, 2025
• Peer Reviewed: Peer Reviewed
• Pages: PC119
• Series Number: 19
• Book Title: Proceedings of The Physiological Society
• Publisher URL: https://www.physoc.org/abstracts/alterations-in-the-autonomic-control-of-heart-rate-and-heart-rate-variability-in-an-ovine-model-of-heart-failure/