Journal article
Parasympathetic dysfunction and antiarrhythmic effect of vagal nerve stimulation following myocardial infarction
JCI insight, Vol.2(16), e86715
08/17/2017
DOI: 10.1172/jci.insight.86715
PMCID: PMC5621871
PMID: 28814663
Abstract
Myocardial infarction causes sympathetic activation and parasympathetic dysfunction, which increase risk of sudden death due to ventricular arrhythmias. Mechanisms underlying parasympathetic dysfunction are unclear. The aim of this study was to delineate consequences of myocardial infarction on parasympathetic myocardial neurotransmitter levels and the function of parasympathetic cardiac ganglia neurons, and to assess electrophysiological effects of vagal nerve stimulation on ventricular arrhythmias in a chronic porcine infarct model. While norepinephrine levels decreased, cardiac acetylcholine levels remained preserved in border zones and viable myocardium of infarcted hearts. In vivo neuronal recordings demonstrated abnormalities in firing frequency of parasympathetic neurons of infarcted animals. Neurons that were activated by parasympathetic stimulation had low basal firing frequency, while neurons that were suppressed by left vagal nerve stimulation had abnormally high basal activity. Myocardial infarction increased sympathetic inputs to parasympathetic convergent neurons. However, the underlying parasympathetic cardiac neuronal network remained intact. Augmenting parasympathetic drive with vagal nerve stimulation reduced ventricular arrhythmia inducibility by decreasing ventricular excitability and heterogeneity of repolarization of infarct border zones, an area with known proarrhythmic potential. Preserved acetylcholine levels and intact parasympathetic neuronal pathways can explain the electrical stabilization of infarct border zones with vagal nerve stimulation, providing insight into its antiarrhythmic benefit.
Direct neuronal recordings and neurotransmitter measurements demonstrate that myocardial infarction reduces parasympathetic drive, which can be modulated by vagal nerve stimulation to control ventricular tachycardia.
Details
- Title: Subtitle
- Parasympathetic dysfunction and antiarrhythmic effect of vagal nerve stimulation following myocardial infarction
- Creators
- Marmar Vaseghi - University of California, Los AngelesSiamak Salavatian - University of California, Los AngelesPradeep S. Rajendran - University of California, Los AngelesDaigo Yagishita - Texas Cardiac ArrhythmiaWilliam R. Woodward - University of PortlandDavid Hamon - Texas Cardiac ArrhythmiaKentaro Yamakawa - University of PortlandTadanobu Irie - Texas Cardiac ArrhythmiaBeth A. Habecker - Oregon Health & Science UniversityKalyanam Shivkumar - University of California, Los Angeles
- Resource Type
- Journal article
- Publication Details
- JCI insight, Vol.2(16), e86715
- Publisher
- American Society for Clinical Investigation
- DOI
- 10.1172/jci.insight.86715
- PMID
- 28814663
- PMCID
- PMC5621871
- ISSN
- 2379-3708
- eISSN
- 2379-3708
- Language
- English
- Date published
- 08/17/2017
- Academic Unit
- Internal Medicine
- Record Identifier
- 9984694748802771
Metrics
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