Sympathetic and vagus nerve stimulation exert positive and negative responses in heart rate (HR) respectively. They modulate ventricular fibrillation threshold (VFT) and action potential duration restitution (RT), both of which are markers of ventricular arrhythmia vulnerability. Prominent features of heart failure (HF) are sympathetic overdrive, parasympathetic attenuation and left ventricular (LV) impairment yet confirmation of autonomic imbalance in an in-vitro model is lacking. Our aim was to assess the effect of autonomic nerve stimulation on HR, atrio-ventricular delay (AVD), VFT and RT in an in-vitro innervated heart preparation following coronary ligation induced HF. Coronary ligation (HF; n=13) and sham (SHM; n=12) surgeries were performed using NZW rabbits following anaesthesia (ketamine, 10mg/kg; medetomidine hydrochloride, 0.2mg/kg; butorphanol, 0.05mg/kg; s/c). After 6 weeks recovery, transthoracic echocardiography was performed to measure LV ejection fraction (EF) and fractional area change (FAC). Following 8 weeks recovery, terminal in-vitro experiments were performed using the dual-innervated Langendorff perfused heart preparation obtained after anaesthesia (ketaset; sedator and torbugesic; doses as above; s.c), propofol anaesthesia and euthanasia using sodium pentobarbitone (160mg/kg). The effect of nerve stimulation was determined from within the spinal cord at the level of the stellate ganglia (SS) and the right cervical vagus nerve (VS). HR responses were examined during stimulation between 0-20Hz, whilst AVD was measured during atrial pacing (300ms CL) at 10Hz (SS) and 5Hz (VS). VFT, defined as the minimum current inducing sustained VF by burst pacing and RT slope, determined using an extrastimulus protocol, were performed at nerve frequencies for equivalent HR response (SS: HF-9Hz; SHM-8Hz / VS: HF-11Hz; SHM-8Hz). Data are mean±SEM, *P<0.05 taken as significant. EF (28.8±1.3 [HF] vs. 53.6±2.4% [SHM]) and FAC (27.0±2.8 [HF] vs. 51.2±2.5% [SHM]) were lower in HF. In HF, sympathetic tachycardia was significantly exaggerated whilst the vagal bradycardia was attenuated at high frequencies (Fig 1A). SS-AVD shortening (-9.4±1.9 (HF) vs. -19.5±3.0ms [SHM]) and VS-AVD prolongation (11.4±3.1 [HF] vs. 42.7±7.7ms [SHM]) were both significantly attenuated in HF. VFT was lower in HF during SS and VS (Fig 1B). RT was significantly steeper during SS (4.3±0.3 [HF] vs. 3.2±0.2 [SHM]) and VS (0.9±0.1 [HF] vs. 0.6±0.1 [SHM]) respectively. Coronary ligation-induced HF in rabbits leads to adverse electro-mechanical remodeling as well as an abnormal autonomic phenotype characterized by exaggerated SS and attenuated VS responses at atrial and ventricular level, providing a basis for ventricular arrhythmia in HF.