title: Central-peripheral neural network interactions evoked by vagus nerve stimulation: functional consequences on control of cardiac function.
abstract: Using vagus nerve stimulation (VNS), we sought to determine the contribution of vagal afferents to efferent control of cardiac function. In anesthetized dogs, the right and left cervical vagosympathetic trunks were stimulated in the intact state, following ipsilateral or contralateral vagus nerve transection (VNTx), and then following bilateral VNTx. Stimulations were performed at currents from 0.25 to 4.0 mA, frequencies from 2 to 30 Hz, and a 500-μs pulse width. Right or left VNS evoked significantly greater current- and frequency-dependent suppression of chronotropic, inotropic, and lusitropic function subsequent to sequential VNTx. Bradycardia threshold was defined as the current first required for a 5% decrease in heart rate. The threshold for the right vs. left vagus-induced bradycardia in the intact state (2.91 ± 0.18 and 3.47 ± 0.20 mA, respectively) decreased significantly with right VNTx (1.69 ± 0.17 mA for right and 3.04 ± 0.27 mA for left) and decreased further following bilateral VNTx (1.29 ± 0.16 mA for right and 1.74 ± 0.19 mA for left). Similar effects were observed following left VNTx. The thresholds for afferent-mediated effects on cardiac parameters were 0.62 ± 0.04 and 0.65 ± 0.06 mA with right and left VNS, respectively, and were reflected primarily as augmentation. Afferent-mediated tachycardias were maintained following β-blockade but were eliminated by VNTx. The increased effectiveness and decrease in bradycardia threshold with sequential VNTx suggest that 1) vagal afferents inhibit centrally mediated parasympathetic efferent outflow and 2) the ipsilateral and contralateral vagi exert a substantial buffering capacity. The intact threshold reflects the interaction between multiple levels of the cardiac neural hierarchy.
authors.affiliation: Neurocardiology Research Center of Excellence, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California; Cardiac Arrhythmia Center, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California; Molecular, Cellular, and Integrative Physiology Program, University of California-Los Angeles, Los Angeles, California; jardell@mednet.ucla.edu.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Ardell
authors.affiliation: Neurocardiology Research Center of Excellence, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California; Cardiac Arrhythmia Center, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California; Molecular, Cellular, and Integrative Physiology Program, University of California-Los Angeles, Los Angeles, California;
authors.forename: Pradeep S
authors.initials: PS
authors.lastname: Rajendran
authors.affiliation: Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee; and.
authors.forename: Heath A
authors.initials: HA
authors.lastname: Nier
authors.affiliation: Cyberonics Inc., Houston, Texas.
authors.forename: Bruce H
authors.initials: BH
authors.lastname: KenKnight
authors.affiliation: Neurocardiology Research Center of Excellence, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California; Cardiac Arrhythmia Center, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California;
authors.forename: J Andrew
authors.initials: JA
authors.lastname: Armour
mesh_terms: D000344:Afferent Pathways / Q000502:physiology*; D000818:Animals; D001919:Bradycardia / Q000503:physiopathology; D004285:Dogs; D004525:Efferent Pathways / Q000502:physiology*; D005260:Female; D006321:Heart / Q000294:innervation*; D006339:Heart Rate / Q000502:physiology*; D008297:Male; D010275:Parasympathetic Nervous System / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000502:physiology*; D013610:Tachycardia / Q000503:physiopathology; D014630:Vagus Nerve / Q000502:physiology*; D055536:Vagus Nerve Stimulation
keywords: afferent; autonomic nervous system; intrinsic cardiac nervous system; parasympathetic; vagus nerve stimulation