Reduced epicardial vagal nerve density and impaired vagal control in a rat myocardial infarction–heart failure model

• DOI: 10.1016/j.carpath.2016.10.003
• Publication Date: 2016-10-23T13:45:17Z
• Authors: Matthew S. Delfiner; John Siano; Ying Li; Eduard I. Dedkov; Youhua Zhang
• Keywords: Heart Failure; Male; Myocardial Infarction; Vagus Nerve; Autonomic Nervous System; Immunohistochemistry; Rats; 3. Good health; Rats, Sprague-Dawley; Disease Models, Animal; 03 medical and health sciences; 0302 clinical medicine; Acetylcholinesterase; Animals; Female; Pericardium

Autonomic remodeling, 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 causes epicardial autonomic nerve remodeling is unknown.Myocardial infarction (MI) was produced in 14 Sprague-Dawley rats, and 10 sham surgery rats served as the control. MI-HF was confirmed 2 months after the surgery by echocardiography and hemodynamic measurement. Cervical vagal nerve stimulation was delivered to examine the heart rate slowing effect. Whole heart acetylcholinesterase histochemistry was used to examine the epicardial autonomic nerve remodeling at dorsal ventricles (remote from the infarcted area). Compared with the control animals, the same vagal nerve stimulation had less heart rate slowing effect in MI-HF group. Both epicardial nerve bundle length-density (2.56±0.60 μm/mm2 versus 1.68±0.46 μm/mm2, P=.001) and branching point-density (1.24±0.25 points/mm2 versus 0.66±0.18 points/mm2, P<.001) were lower in MI-HF rats. The chemically stained epicardial nerve bundles contain both sympathetic (tyrosine hydroxylase positive) and vagal (choline acetyltransferase positive) fibers. However, within the stained nerve bundle, the chemical color corresponds mainly with the vagal fibers.Whole heart acetylcholinesterase histochemistry revealed a decreased ventricular epicardial vagal nerve density in MI-HF rats, which may contribute to impaired cardiac vagal control in HF.