Myocardial infarction reduces cardiac nociceptive neurotransmission through the vagal ganglia
Siamak Salavatian, Jonathan D. Hoang, Naoko Yamaguchi, Zulfiqar Ali Lokhandwala, Mohammed Amer Swid, John Andrew Armour, Jeffrey L. Ardell, Marmar Vaseghi
Siamak Salavatian, Jonathan D. Hoang, Naoko Yamaguchi, Zulfiqar Ali Lokhandwala, Mohammed Amer Swid, John Andrew Armour, Jeffrey L. Ardell, Marmar Vaseghi
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Research Article Cardiology Neuroscience

Myocardial infarction reduces cardiac nociceptive neurotransmission through the vagal ganglia

Abstract

Myocardial infarction causes pathological changes in the autonomic nervous system, which exacerbate heart failure and predispose to fatal ventricular arrhythmias and sudden death. These changes are characterized by sympathetic activation and parasympathetic dysfunction (reduced vagal tone). Reasons for the central vagal withdrawal and, specifically, whether myocardial infarction causes changes in cardiac vagal afferent neurotransmission that then affect efferent tone, remain unknown. The objective of this study was to evaluate whether myocardial infarction causes changes in vagal neuronal afferent signaling. Using in vivo neural recordings from the inferior vagal (nodose) ganglia and immunohistochemical analyses, structural and functional alterations in vagal sensory neurons were characterized in a chronic porcine infarct model and compared with normal animals. Myocardial infarction caused an increase in the number of nociceptive neurons but a paradoxical decrease in functional nociceptive signaling. No changes in mechanosensitive neurons were observed. Notably, nociceptive neurons demonstrated an increase in GABAergic expression. Given that nociceptive signaling through the vagal ganglia increases efferent vagal tone, the results of this study suggest that a decrease in functional nociception, possibly due to an increase in expression of inhibitory neurotransmitters, may contribute to vagal withdrawal after myocardial infarction.

Authors

Siamak Salavatian, Jonathan D. Hoang, Naoko Yamaguchi, Zulfiqar Ali Lokhandwala, Mohammed Amer Swid, John Andrew Armour, Jeffrey L. Ardell, Marmar Vaseghi

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Figure 8

Upregulation of inhibitory GABAergic neurotransmission specifically in CGRP-expressing nodose ganglia neurons involved in nociceptive neurotransmission.

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Upregulation of inhibitory GABAergic neurotransmission specifically in C...
(A) Representative images of nodose ganglia from normal (N; left) and LAD-infarcted (MI; right) animals stained for GAD2 (blue) and CGRP (purple). (B) Top, summary of the percentage of GAD2+ neurons as a subset of all neurons, CGRP+ neurons, and CGRP– neurons is shown. Although overall expression of GAD2 was unchanged between normal and LAD-infarcted animals (P = 0.80), the percentage of neurons that coexpress both GAD2 and CGRP was increased after MI (P = 0.04 for LAD-infarcted vs. normal animals). Coexpression of GAD2 was decreased in neurons that do not express CGRP (P = 0.006 for normal vs. LAD-infarcted animals). n = 5 pigs per group. Bottom, summary of the percentage of GABA+ neurons as a subset of all neurons, CGRP+ neurons, and CGRP– neurons is shown. Similar to GAD2, GABA showed no overall difference (P = 0.57) while its expression in CGRP+ neurons was increased (P = 0.02) in MI animals. However, expression of GABA in CGRP– neurons was similar between normal and MI animals (P = 0.89). (C) Representative images of nodose ganglia from normal (left) and LAD-infarcted (right) pigs stained for GABA type B receptor subunit 1 (GABBR1) (green) and CGRP (purple). There was no difference in the expression of GABBR1. n = 5 pigs per group. (D) Summary of the percentage of CGRP+ neurons with GABBR1+ expression (P = 0.21). n = 10 for normal and n = 7 for MI animals. Data are shown as mean ± SEM; unpaired, 2-tailed Student’s t test. Scale bars are 50 μm.