Vagus nerve stimulation mitigates intrinsic cardiac neuronal and adverse myocyte remodeling postmyocardial infarction.
This paper aims to determine whether chronic vagus nerve stimulation (VNS) mitigates myocardial infarction (MI)-induced remodeling of the intrinsic cardiac nervous system (ICNS), along with the cardiac tissue it regulates. Guinea pigs underwent VNS implantation on the right cervical vagus. Two weeks later, MI was produced by ligating the ventral descending coronary artery. VNS stimulation started 7 days post-MI (20 Hz, 0.9 ± 0.2 mA, 14 s on, 48 s off; VNS-MI, n = 7) and was compared with time-matched MI animals with sham VNS (MI n = 7) vs. untreated controls (n = 8). Echocardiograms were performed before and at 90 days post-MI. At termination, IC neuronal intracellular voltage recordings were obtained from whole-mount neuronal plexuses. MI increased left ventricular end systolic volume (LVESV) 30% (P = 0.027) and reduced LV ejection fraction (LVEF) 6.5% (P < 0.001) at 90 days post-MI compared with baseline. In the VNS-MI group, LVESV and LVEF did not differ from baseline. IC neurons showed depolarization of resting membrane potentials and increased input resistance in MI compared with VNS-MI and sham controls (P < 0.05). Neuronal excitability and sensitivity to norepinephrine increased in MI and VNS-MI groups compared with controls (P < 0.05). Synaptic efficacy, as determined by evoked responses to stimulating input axons, was reduced in VNS-MI compared with MI or controls (P < 0.05). VNS induced changes in myocytes, consistent with enhanced glycogenolysis, and blunted the MI-induced increase in the proapoptotic Bcl-2-associated X protein (P < 0.05). VNS mitigates MI-induced remodeling of the ICNS, correspondingly preserving ventricular function via both neural and cardiomyocyte-dependent actions.
Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee;
Eric
E
Beaumont
Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee;
Elizabeth M
EM
Southerland
Department of Biology, Ithaca College, Ithaca, New York;
Jean C
JC
Hardwick
Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee;
Gary L
GL
Wright
Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee;
Shannon
S
Ryan
Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee;
Ying
Y
Li
Cyberonics, Houston, Texas; and.
Bruce H
BH
KenKnight
Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee; Department of Medicine, University of California Los Angeles Health System, Los Angeles, California.
J Andrew
JA
Armour
Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee; Department of Medicine, University of California Los Angeles Health System, Los Angeles, California jardell@mednet.ucla.edu.
Jeffrey L
JL
Ardell
D000818:Animals; D001341:Autonomic Nervous System / Q000503:physiopathology*; D005071:Evoked Potentials; D050261:Glycogenolysis; D006168:Guinea Pigs; D006321:Heart / Q000294:innervation*; D008564:Membrane Potentials; D009203:Myocardial Infarction / Q000503:physiopathology*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000502:physiology*; D009638:Norepinephrine / Q000378:metabolism; D013318:Stroke Volume / Q000502:physiology; D009435:Synaptic Transmission; D055536:Vagus Nerve Stimulation; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology*; D016277:Ventricular Function, Left; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D051028:bcl-2-Associated X Protein; D009638:Norepinephrine
autonomic regulation therapy; guinea pig; intrinsic cardiac nervous system; myocardial infarction; vagus nerve stimulation