Parasympathetic dysfunction and antiarrhythmic effect of vagal nerve stimulation following myocardial infarction
Marmar Vaseghi, … , Beth A. Habecker, Kalyanam Shivkumar
Marmar Vaseghi, … , Beth A. Habecker, Kalyanam Shivkumar
Published August 17, 2017
Citation Information: JCI Insight. 2017;2(16):e86715. https://doi.org/10.1172/jci.insight.86715.
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Research Article Cardiology

Parasympathetic dysfunction and antiarrhythmic effect of vagal nerve stimulation following myocardial infarction

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.

Authors

Marmar Vaseghi, Siamak Salavatian, Pradeep S. Rajendran, Daigo Yagishita, William R. Woodward, David Hamon, Kentaro Yamakawa, Tadanobu Irie, Beth A. Habecker, Kalyanam Shivkumar

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Figure 1

Cardiac voltage mapping and neurotransmitter analysis.

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Cardiac voltage mapping and neurotransmitter analysis. (A) Bipolar volta...
(A) Bipolar voltage electroanatomic maps of infarcted hearts were obtained and used to identify viable, border zone, and scar regions. Examples of bipolar electrical recordings from viable, border zone, and scar regions are shown. Examples of uinpolar electrograms obtained from similar regions are also shown. This map and bipolar voltage measurements were used to obtain samples for neurotransmitter analysis from appropriate locations. The scale bar shows the voltage from 0–10 mV. (B) In normal hearts (n = 12 normal animals, 3 samples per animal), acetylcholine (ACh) levels were not significantly different on the LV apex, anterior, lateral walls (linear mixed effects model). (C) ACh levels from paired LV epicardium and endocardium samples were also not significantly different (n = 9 normal animals, 2–3 samples per animal). (D) In infarcted hearts (n = 14), scar regions have the lowest ACh content compared with viable and border zone regions (P < 0.01, linear mixed effects model, 1–3 samples per region per animal). However, ACh content between viable and border zone regions of infarcted animals (n = 14) compared with similar regions of normal hearts (n = 15 animals) was not statistically significant (P = 0.4, linear mixed effects model). There is a suggestion that scar ACh may be somewhat reduced compared with normal hearts; however, this difference did not reach statistical significance. (E) Similar to ACh levels, there was no difference in norepinephrine (NE) content across the LV apex, anterior, or lateral wall (linear mixed effects model, n = 12 normal animals, 3 samples per animal). (F) Also, similar to ACh, NE levels in the endocardium were similar to epicardium (linear mixed effects model, n = 9 animals, 2–3 samples per animal). (G) Unlike ACh, the NE content in scar and border zone regions was significantly reduced compared with viable myocardium in infarcted hearts (P < 0.05 for border zone vs. viable, and P < 0.01 for scar vs. viable, linear mixed effects model, n = 5 animals, 1–3 samples per region per animal) and was significantly less than similar regions in normal hearts (P < 0.01, linear mixed effects model). There was no difference in NE content of viable regions of infarcted hearts compared with normal hearts. MI, myocardial infarction; EGM, myocardial electrogram; LV, left ventricle; Epi, epicardium; Endo, endocardium.