Characterization of neuronal discharge in the thoracic spinal cord during cardiac stress in a porcine model

Abstract

Sudden cardiac death is the leading cause of death in the United States and is often caused by ventricular tachyarrhythmias (VT; Mozaffarian et al., 2015). Myocardial ischemia triggers imbalances in sympathetic and parasympathetic modulation, via the autonomic nervous system, and leads to the pathophysiology of cardiac arrhythmias. However, the spinal mechanism of this sympathetic neural control remains poorly understood. We hypothesize that cardiac stressors elicit distinct neural signatures in the dorsal horn (DH; the spinal relay point for cardiac afferents) and the intermediolateral (IML) nucleus of the thoracic spinal cord (the primary nexus for modulation of sympathetic efferent outflow). Adult, anesthetized Yorkshire pigs (n=9; 42 ± 1.6 kg) were implanted with high‐density microarrays (64–256 electrodes; Neuronexus) in the thoracic spinal cord to record extracellular potentials. Antidromic stimulation of the T2 paravertebral chain allowed identification of sympathetic preganglionic neurons located in the IML (53 of total 1,757 neurons recorded). To characterize neuronal discharge, after a baseline recording, pigs repeatedly received: 1) chest scratch (SCR), 2) heart touch (THR), 3) ligation of the left anterior descending coronary artery (LAD), 4) occlusion of the inferior vena cava (IVC), or 5) occlusion of the descending aorta (AOC). Preliminary investigation of percent change in firing rate from baseline suggests complex neural signatures in DH and IML neurons during perturbations. A subset of DH neurons increased firing rate during SCR (8.29% of DH neurons), THR (10.70%), LAD (14.40%), IVC (21.57%), and AOC (6.13%). Firing rate increased in a subset of IML neurons as well (3.84% during SCR, 26.92% during THR, 18.87% during LAD, 20.75% during IVC, and 12.12% during AOC). In contrast, firing rate decreased in 4.89% of DH neurons during SCR, 20.88% during THR, 21.63% during LAD, 16.44% during IVC, and 9.85% during AOC. Additionally, rates decreased in a small population of IML neurons (3.84% during SCR, 7.69% during THR, 28.30% during LAD, 5.66% during IVC, and 18.18% during AOC). Subsequent analysis revealed positive correlations between DH and IML neurons, indicating excitatory neuronal connectivity. Further investigation is warranted to understand the temporally related discharge patterns as well as the inhibitory or excitatory nature of these connections. These preliminary data pave a potential pathway to develop targeted neuraxial interventions in cases of intractable ventricular arrhythmia.Support or Funding InformationHL084261, T32‐HD043730This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.