Spinal cord neural network interactions: implications for sympathetic control of the porcine heart

Abstract

Inherent and acquired factors determine the integrated autonomic response to cardiovascular stressors. Excessive sympathoexcitation to ischemic stress is a major contributor to the potential for sudden cardiac death. To define fundamental aspects of cardiac-related autonomic neural network interactions within the thoracic cord, specifically as related to modulating sympathetic preganglionic (SPN) neural activity. Adult, anesthetized Yorkshire pigs ( n = 10) were implanted with penetrating high-density microarrays (64 electrodes) at the T2 level of the thoracic spinal cord to record extracellular potentials concurrently from left-sided dorsal horn (DH) and SPN neurons. Electrical stimulation of the T2 paravertebral chain allowed for antidromic identification of SPNs located in the intermediolateral cell column (57 of total 1,760 recorded neurons). Cardiac stressors included epicardial touch, occlusion of great vessels to transiently alter preload/afterload, and transient occlusion of the left anterior descending coronary artery (LAD). Spatial/temporal assessment of network interactions was characterized by cross-correlation analysis. While some DH neurons responded solely to changes in preload/afterload (8.5 ± 1.9%) or ischemic stress (10.5 ± 3.9%), the majority of cardiovascular-related DH neurons were multimodal (30.2 ± 4.7%) with ischemia sensitivity being one of the modalities (26.1 ± 4.7%). The sympathoexcitation associated with transient LAD occlusion was associated with increased correlations from baseline within DH neurons (2.43 ± 0.61 to 7.30 ± 1.84%, P = 0.04) and between SPN to DH neurons (1.32 ± 0.78 to 7.24 ± 1.84%, P = 0.02). DH to SPN network correlations were reduced during great vessel occlusion. In conclusion, increased intrasegmental network coherence within the thoracic spinal cord contributes to myocardial ischemia-induced sympathoexcitation. NEW & NOTEWORTHY In an in vivo pig model, we demonstrate using novel high-resolution neural electrode arrays that increased intrasegmental network coherence within the thoracic spinal cord contributes to myocardial ischemia-induced sympathoexcitation.

Neuromodulation With Thoracic Dorsal Root Ganglion Stimulation Reduces Ventricular Arrhythmogenicity

“…In two pigs, this protocol was performed for both 20 Hz and 1 k Hz, where enough time was allowed to return to the baseline condition before repeating the protocol for another stimulation parameter. We have previously extensively characterized this experimental animal model (Batul et al, 2017;Howard-Quijano et al, 2017b;Dale et al, 2020;Omura et al, 2021). In brief, animals were sedated with telazol (4 mg/kg, intramuscular) and xylazine (2 mg/kg, intramuscular) and mechanically ventilated by tracheal intubation (Omura et al, 2021).…”

“…Subsequent to this, a median sternotomy was performed in the supine position to expose the heart. After the completion of surgical preparation, general anesthesia was transitioned to intravenous alpha-chloralose (50 mg/kg initial bolus followed by a 20 mg/kg/h continuous infusion), which limits the impact on cardiac myocardial electrophysiology (Batul et al, 2017;Howard-Quijano et al, 2017b;Dale et al, 2020;Omura et al, 2021). The depth of anesthesia was assessed throughout the experiments by monitoring corneal reflexes, jaw tone, and hemodynamic indices.…”

“…Spinal cord neural networks are modified by afferent transduction from cardiopulmonary sensory neurites from the DRG neurons (Barman and Yates, 2017;Dale et al, 2020;Omura et al, 2021); therefore, bioelectronic DRGS has the potential to directly modulate the dorsal root and dorsal horn neurons and indirectly modulate the spinal preganglionic neurons that innervate the heart. While DRGS for neuropathic pain has been examined, the effects and roles of DRGS in the treatment of cardiac arrhythmias are not known.…”

Spinal Anesthesia Reduces Myocardial Ischemia–triggered Ventricular Arrhythmias by Suppressing Spinal Cord Neuronal Network Interactions in Pigs

“…the intrinsic cardiac neuronal network to regulate, beat by beat, regional cardiac function. 1,2,[5][6][7] Acute myocardial ischemia significantly increases spinal sympathoexcitation and intrinsic cardiac neuronal activity contributing to arrhythmias. 4,5,[8][9][10] Spinal interventions (pharmacologic and electrical) not only provide anesthesia but also modulate spinal cord sympathetic output and have been shown to be cardioprotective in animals and humans.…”

“…To understand these complex neural interactions, we have recently developed novel techniques for simultaneous recordings of cardiac electrophysiology/function and spinal cord neuronal network activity in the dorsal horn (afferent) and intermediolateral (efferent) regions with high-resolution, high-fidelity electrode microarrays. 7 Previous work has focused primarily on recordings of the single-unit activity of spinal neurons that do not describe neural network interactions. 23,24 The primary outcome of this study was to determine the alteration in spinal cord neuronal network interactions associated with the cardioprotective effects of spinal anesthesia during acute myocardial ischemia.…”