Abstracts / Autonomic Neuroscience: Basic and Clinical 192 (2015) 56–141
signiﬁcant differences were observed in the basal levels of renal sympathetic nerve activity (117 ± 16 vs. 120 ± 9 spikes/sec, p N 0.05) and mean arterial pressure (70 ± 4 vs. 77 ± 6 mmHg, p N 0.05) between control group and ivabradine. The results indicate that the bradycardia evoked by chronic treatment with ivabradine did not interfere on the renal sympathetic nerve activity and arterial blood pressure. The current study suggests that long term treatment with ivabradine reduce heart rate without significant side effects on the sympathetic activity. Supported by Capes, CNPq and Fapemig.
P5.14 Cardiac arrhythmias during or after epileptic seizures M. van der Lendea,b, R. Surgesc, J.W. Sandera,d, R.D. Thijsa,b,d a Stichting Epilepsie Instellingen Nederland (SEIN), Heemstede, The Netherlands b Department of Neurology, Leiden University Medical Center (LUMC), Leiden, The Netherlands c Department of Epileptology, University of Bonn Medical Center, Bonn, Germany d NIHR University College London Hospitals Biomedical Research Centre, Department of Clinical & Experimental Epilepsy, London, and Epilepsy Society, Chalfont St Peter, UK Aim: Seizure-related cardiac arrhythmias are frequently reported and have been implicated as potential pathomechanisms of Sudden Unexpected Death in Epilepsy (SUDEP). We attempted to identify clinical proﬁles associated with various (post)ictal cardiac arrhythmias. Methods: We conducted a systematic search from the ﬁrst date available to July 2013 on the combination of two terms: “cardiac arrhythmias” and “epilepsy”. Databases searched were PubMed, Embase (OVID version), Web of Science and COCHRANE Library. We looked for case reports and case series. Results: We identiﬁed seven distinct (post)ictal cardiac arrhythmias: ictal asystole (103 cases), postictal asystole (13 cases), ictal bradycardia (25 cases), ictal AV-conduction block (11 cases), postictal AVconduction block (2 cases), (post)ictal atrial ﬂutter/atrial ﬁbrillation (14 cases) and postictal ventricular ﬁbrillation (3 cases). Ictal asystole had a mean prevalence of 0.38% (SD = 0.04) in people with refractory epilepsy. Ictal asystole, bradycardia and AV-conduction block were self-limiting in all but one case and seen during complex partial seizures. Seizure onset was mostly temporal (91%) without consistent lateralization. By contrast, postictal cardiac arrhythmias were mostly found following a convulsive seizure (92%) and were frequently associated with (near) SUDEP (35%). onclusion: The contrasting clinical proﬁles of ictal and postictal arrhythmias suggest different pathomechanisms. Postictal rather than ictal arrhythmias seem of greater importance to the pathophysiology of SUDEP.
P5.15 The sympathetic co-transmitter Neuropeptide Y is a novel pro-arrhythmic trigger even in the presence of maximal beta-blockade M. Kalla, G. Bub, R. Burton, H. Larsen, D.J. Paterson, N. Herring BHF Centre of Research Excellence, Department of Physiology, Anatomy
and Genetics, University of Oxford, Sherrington Building, Parks Road, Oxford, UK, OX1 3PT Purpose: Beta-blockers (BB) are the only anti-arrhythmic drugs that improve mortality post myocardial infarction, but a signiﬁcant risk of arrhythmia remains. During high-level sympathetic stimulation (SS), such as during MI, co-transmitters including neuropeptide Y (NPY) are released with norepinephrine. We investigated whether NPY is independently pro-arrhythmic, and hypothesised that ventricular ﬁbrillation threshold (VFT) would still be reduced following high-level SS even in the presence of a BB. Methods and Results: Hearts with intact stellate ganglia (SG) from SD rats were Langendorff perfused. Two minutes of right (n = 6) or left (n = 6) SG stimulation in the presence of metoprolol (10 μM) signiﬁcantly reduced VFT (RSG: 2 ± 0.44 vs. 1 ± 0.24 mA) and caused the release of NPY into perfusate (detected by ELISA, n = 6). Exogenous NPY (250nM, n = 6) also signiﬁcantly reduced VFT (2.4 ± 0.15 vs 1.2 ± 0.12 mA), an effect abolished by Y1 receptor blockade (BIBO3304, 1 μM, n = 6), but not Y2 blockade (BIIE0246 1 μM, n = 6). Addition of NPY during optical mapping demonstrated steepening of the action potential duration (APD) restitution curve (0.27 ± 0.04, NPY 0.42 ± 0.12, n = 4). NPY also increased spontaneous activity in cultured monolayers of ventricular myocytes assessed by dye-free macroscopic optical imaging (6.6 ± 1.24 to 13.5 ± 1.4 active regions, n = 11) and this could also be prevented by Y1 receptor blockade (n = 6). Western blotting and immunohistochemistry conﬁrmed the presence of Y1 receptors on ventricular myocytes. Conclusion: Prolonged sympathetic stimulation remains pro-arrhythmic in the presence of BB, implicating sympathetic co-transmitters as a novel arrhythmic trigger. NPY can directly decrease VFT via a Y1 receptor mediated mechanism, which increases spontaneous activity and steepens APD restitution.
P5.16 Heart failure reduces epicardial autonomic nerve density M. Delﬁner, E. Dedkov, Y. Li, Y. Zhang Department of Biomedical Sciences, New York Institute of Technology College of Osteopathic Medicine, USA Background: Cardiac autonomic dysfunction, characterized by sympathetic activation and vagal withdrawal, contributes to heart failure (HF) progression. However, the exact mechanism(s) responsible for vagal withdrawal in HF remain(s) unclear, and whether HF affects intrinsic epicardial autonomic innervation is unknown. The aim of the study is to investigate the intrinsic epicardial autonomic nerve remodeling in HF. Methods: Large myocardial infarction (MI) was produced in 6 Sprague-Dawley rats by permanent ligation of the left anterior descending coronary artery, and 10 sham-operated rats were used as a control. MI-induced HF was conﬁrmed 2 months after surgery by echocardiography and hemodynamic measurement, and then the hearts were harvested and the intrinsic cardiac autonomic nerves were visualized via acetylcholinesterase histochemistry (Batulevicius D, Annals of Anatomy, 2003; 185: 449-459). Epicardial autonomic innervation of the dorsal atria and ventricles (remote from the infarcted region) was morphometrically analyzed. Results: Both nerve surface density and branching point density were lower in the ventricles of HF rats. The mean ventricular nerve surface density in sham rats was 2.56 mm/mm2 compared to 1.60 mm/mm2 in HF rats (p = 0.008). The mean ventricular nerve branching point density was 1.24 branch points/mm2 in sham rats compared to 0.71 branch points/mm2 in the HF group (p = 0.001). Although there was a trend showing lower nerve