Sympathetic modulation of electrical activation in normal and infarcted myocardium: implications for arrhythmogenesis

Am J Physiol Heart Circ Physiol. 2017 Mar 1;312(3):H608-H621. doi: 10.1152/ajpheart.00575.2016. Epub 2017 Jan 13.

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 CVL nor CVT was 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 & NOTEWORTHY This 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/.

Keywords: autonomic nervous system; conduction velocity; electrical propagation; sympathetic nerves; ventricular arrhythmias.

MeSH terms

  • Animals
  • Arrhythmias, Cardiac / etiology*
  • Arrhythmias, Cardiac / physiopathology*
  • Diffusion Tensor Imaging
  • Electric Stimulation
  • Electrophysiological Phenomena / physiology*
  • Female
  • Heart / diagnostic imaging
  • Heart / physiology*
  • Heart Conduction System / physiology
  • Heart Conduction System / physiopathology
  • Heart Ventricles / innervation
  • Heart Ventricles / physiopathology
  • Immunohistochemistry
  • Male
  • Myocardial Infarction / complications*
  • Myocardial Infarction / diagnostic imaging
  • Myocardial Infarction / physiopathology*
  • Receptors, Adrenergic, beta / drug effects
  • Receptors, Adrenergic, beta / physiology
  • Stellate Ganglion / physiopathology
  • Swine
  • Sympathetic Nervous System / diagnostic imaging
  • Sympathetic Nervous System / physiology*
  • Sympathetic Nervous System / physiopathology*

Substances

  • Receptors, Adrenergic, beta