title: Sympathetic modulation of electrical activation in normal and infarcted myocardium: implications for arrhythmogenesis.
abstract: The influence of cardiac sympathetic innervation on electrical activation in normal and chronically infarcted ventricular myocardium is not understood. Yorkshire pigs with normal hearts (NL,n= 12) or anterior myocardial infarction (MI,n= 9) underwent high-resolution mapping of the anteroapical left ventricle at baseline and during left and right stellate ganglion stimulation (LSGS and RSGS, respectively). Conduction velocity (CV), activation times (ATs), and directionality of propagation were measured. Myocardial fiber orientation was determined using diffusion tensor imaging and histology. Longitudinal CV (CVL) was increased by RSGS (0.98 ± 0.11 vs. 1.2 ± 0.14m/s,P< 0.001) but not transverse CV (CVT). This increase was abrogated by β-adrenergic receptor and gap junction (GJ) blockade. Neither CVLnor CVTwas increased by LSGS. In the peri-infarct region, both RSGS and LSGS shortened ARIs in sinus rhythm (423 ± 37 vs. 322 ± 30 ms,P< 0.001, and 423 ± 36 vs. 398 ± 36 ms,P= 0.035, respectively) and altered activation patterns in all animals. CV, as estimated by mean ATs, increased in a directionally dependent manner by RSGS (14.6 ± 1.2 vs. 17.3 ± 1.6 ms,P= 0.015), associated with GJ lateralization. RSGS and LSGS inhomogeneously modulated AT and induced relative or absolute functional activation delay in parts of the mapped regions in 75 and 67%, respectively, in MI animals, and in 0 and 15%, respectively, in control animals (P< 0.001 for both). In conclusion, sympathoexcitation increases CV in normal myocardium and modulates activation propagation in peri-infarcted ventricular myocardium. These data demonstrate functional control of arrhythmogenic peri-infarct substrates by sympathetic nerves and in part explain the temporal nature of arrhythmogenesis.NEW & NOTEWORTHYThis study demonstrates regional control of conduction velocity in normal hearts by sympathetic nerves. In infarcted hearts, however, not only is modulation of propagation heterogeneous, some regions showed paradoxical conduction slowing. Sympathoexcitation altered propagation in all infarcted hearts studied, and we describe the temporal arrhythmogenic potential of these findings.Listen to this article's corresponding podcast at http://ajpheart.podbean.com/e/sympathetic-nerves-and-cardiac-propagation/.
authors.affiliation: Cardiac Arrhythmia Center, University of California, Los Angeles, California; oajijola@mednet.ucla.edu.|Neurocardiology Research Center of Excellence, University of California, Los Angeles, California.
authors.forename: Olujimi A
authors.initials: OA
authors.lastname: Ajijola
authors.affiliation: Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, Utah.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Lux
authors.affiliation: Cardiac Arrhythmia Center, University of California, Los Angeles, California.
authors.forename: Anadjeet
authors.initials: A
authors.lastname: Khahera
authors.affiliation: Cardiac Arrhythmia Center, University of California, Los Angeles, California.
authors.forename: OhJin
authors.initials: O
authors.lastname: Kwon
authors.affiliation: Department of Radiology, University of California, Los Angeles, California.
authors.forename: Eric
authors.initials: E
authors.lastname: Aliotta
authors.affiliation: Department of Radiology, University of California, Los Angeles, California.
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Ennis
authors.affiliation: Department of Pathology, University of California, Los Angeles, California; and.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Fishbein
authors.affiliation: Cardiac Arrhythmia Center, University of California, Los Angeles, California.|Neurocardiology Research Center of Excellence, University of California, Los Angeles, California.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Ardell
authors.affiliation: Cardiac Arrhythmia Center, University of California, Los Angeles, California.|Neurocardiology Research Center of Excellence, University of California, Los Angeles, California.
authors.forename: Kalyanam
authors.initials: K
authors.lastname: Shivkumar
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology* / Q000503:physiopathology*; D056324:Diffusion Tensor Imaging; D004558:Electric Stimulation; D055724:Electrophysiological Phenomena / Q000502:physiology*; D005260:Female; D006321:Heart / Q000000981:diagnostic imaging / Q000502:physiology*; D006329:Heart Conduction System / Q000502:physiology / Q000503:physiopathology; D006352:Heart Ventricles / Q000294:innervation / Q000503:physiopathology; D007150:Immunohistochemistry; D008297:Male; D009203:Myocardial Infarction / Q000150:complications* / Q000000981:diagnostic imaging / Q000503:physiopathology*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology; D013233:Stellate Ganglion / Q000503:physiopathology; D013552:Swine; D013564:Sympathetic Nervous System / Q000000981:diagnostic imaging / Q000502:physiology* / Q000503:physiopathology*
chemical_list: D011943:Receptors, Adrenergic, beta
keywords: autonomic nervous system; conduction velocity; electrical propagation; sympathetic nerves; ventricular arrhythmias