Cardiac sympathectomy and spinal cord stimulation attenuate reflex-mediated norepinephrine release during ischemia preventing ventricular fibrillation
Jeffrey L. Ardell, … , J. Andrew Armour, Kalyanam Shivkumar
Jeffrey L. Ardell, … , J. Andrew Armour, Kalyanam Shivkumar
Published October 31, 2019
Citation Information: JCI Insight. 2019;4(23):e131648. https://doi.org/10.1172/jci.insight.131648.
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Research Article Cardiology Neuroscience

Cardiac sympathectomy and spinal cord stimulation attenuate reflex-mediated norepinephrine release during ischemia preventing ventricular fibrillation

Abstract

The purpose of this study was to define the mechanism by which cardiac neuraxial decentralization or spinal cord stimulation (SCS) reduces ischemia-induced ventricular fibrillation (VF). Direct measurements of norepinephrine (NE) levels in the left ventricular interstitial fluid (ISF) by microdialysis, in response to transient (15-minute) coronary artery occlusion (CAO), were performed in anesthetized canines. Responses were studied in animals with intact neuraxes and were compared with those in which the intrathoracic component of the cardiac neuraxes (stellate ganglia) or the intrinsic cardiac neuronal (ICN) system was surgically delinked from the central nervous system and those with intact neuraxes with preemptive SCS (T1–T3). With intact neuraxes, animals with exaggerated NE release due to CAO were at increased risk for VF. During CAO, there was a 152% increase in NE when the neuraxes were intact compared with 114% following stellate decentralization and 16% following ICN decentralization. During SCS, CAO NE levels increased by 59%. Risk for CAO-induced VF was 38% in controls, 8% following decentralization, and 11% following SCS. These data indicate that ischemia-related afferent neuronal transmission differentially engages central and intrathoracic sympathetic reflexes and amplifies sympathoexcitation. Differences in regional ventricular NE release are associated with increased risk for VF. Surgical decentralization or SCS reduced NE release and VF.

Authors

Jeffrey L. Ardell, Robert D. Foreman, J. Andrew Armour, Kalyanam Shivkumar

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Figure 1

Experimental design.

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Experimental design. Summary of experimental protocol of coronary occlus...
Summary of experimental protocol of coronary occlusion and sites of microdialysis for norepinephrine (NE) collection. The left anterior descending coronary artery (LAD) is shown. The levels of decentralization as related to primary elements of the neural hierarchy for cardiac control are shown. Responses in animals with (a) intact neuraxes (group 1) were compared with those in which the (b) intrathoracic component of the cardiac neuraxes was surgically disconnected from the central nervous system and (c) those with intact neuraxes subjected to SCS (group 4; T1–T3 spinal level). For group 2 decentralization, the cervical vagosympathetic nerve trunks were transected and all connections from the cardiac nervous system to stellate ganglia were transected. For group 3 decentralization, all connections to (efferent) and from (afferent) the heart were surgically interrupted. LCN, local circuit neurons; Sympath, sympathetic; Parasym, parasympathetic; Aff, afferent; T, thoracic spinal segment; C, cervical spinal segment; DRG, dorsal root ganglia; Gs and Gi, stimulatory and inhibitory guanine nucleotide binding protein.