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 3

Functional analysis of nodose neuronal activity following MI.

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Functional analysis of nodose neuronal activity following MI. (A) Creati...
(A) Creation of right coronary artery myocardial infarct. Left panel: representative coronary angiography (RCA) while placing the percutaneous transluminal angioplasty catheter (PTA) in the RCA. The distal radiopaque marker indicates the distal end of the angioplasty catheters where microspheres are injected. Right panel: Coronary artery angiography after RCA infarct creation. Contrast dye was injected into the RCA to confirm the location of the occlusion. (B) Representative magnetic resonance imaging (MRI) images of the RCA-infarcted heart. Scar tissues were confirmed by assessing the thickness and the color of the myocardial regions in the MRI image. (C) Customized 16-channel linear microelectrode array probes were used to record nodose neurons in vivo. (D) The neural probe was inserted in the nodose ganglion. (E) Representative sorted neuronal action potentials for 3 neurons from 1 animal. Action potentials from individual neurons are illustrated in the right panel. Left ventricular pressure (LVP) and electrocardiogram (ECG) were recorded simultaneously with neural recordings. (F) Responses of 97 cardiac nodose neurons from 11 normal animals (8.8 ± 2.1 per animal) to epicardial mechanical stimulation (EMS), epicardial nociceptive stimuli (NS), aortic occlusion (AO), inferior vena cava (IVC) occlusion, and ventricular pacing (VP). Only significant responses (P < 0.05) to each stressor based on the Skellam test are shown. (G) The response of 133 cardiac nodose neurons from 11 animals with MI involving the RCA to cardiac stressors are shown. (H) Nodose neuronal firing rate at baseline. There was no difference in the basal activity of nodose neurons in normal versus MI animals. There was no difference in the activity of neurons from the left versus right nodose ganglia. (n = 37, 56, 63, and 62 for normal-left nodose, normal-right nodose, MI-left nodose, and MI-right nodose ganglia, respectively.) Median and 95% confidence intervals are shown, and Mann-Whitney U statistical test was used for comparisons.