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 1

Assessment of expression profiles of left versus right nodose ganglia neurons in normal and LAD-infarcted animals.

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Assessment of expression profiles of left versus right nodose ganglia ne...
(A) Creation of myocardial infarct in the LAD distribution. Left panel: representative coronary angiography. Middle panel: Coronary artery angiography after microsphere injection showing occlusion at the mid-LAD. Right panel: Representative gross image of an infarcted heart showing scar in the region vascularized by the LAD. (B) Nodose ganglia from normal and infarcted animals were removed and analyzed for immunohistochemical changes. Scale bars are 5 mm (top), 50 μm (bottom). (C) Percentages of nodose ganglia neurons from normal and (D) infarcted (MI) animals expressing P2RX3, CGRP, PIEZO2, and NOS1 were quantified. No difference in the expression profiles of neurons between the left and right nodose ganglia was found in either normal or infarcted animals for P2RX3 (normal left vs. right nodose: P = 0.82; MI left vs. right nodose: P = 0.67), CGRP (normal left vs. right nodose: P = 0.82; MI left vs. right nodose: P = 0.89), PIEZO2 (a mechanosensitive ion channel; normal left vs. right nodose: P = 0.97; MI left vs. right nodose: P = 0.67), or NOS1 (normal left vs. right nodose: P = 0.82; MI left vs. right nodose: P = 0.67). n = 6 pairs of nodose for P2RX3 in normal animals and CGRP in both normal and MI animals. n = 5 pairs of nodose ganglia for PIEZO2 in normal and MI animals. n = 8 pairs of nodose ganglia for NOS1 in normal and MI animals. Data shown as mean  ±  SEM; paired, 2-tailed Student’s t test with the false discovery rate corrected by the Benjamini-Hochberg method was used for analyses. CGRP, calcitonin gene-related peptide; LV, left ventricle; NOS1, nitric oxide synthase 1; P2RX3, P2X purinoceptor 3; RV, right ventricle.