Abstract
Stellate ganglia within the intrathoracic cardiac control system receive and integrate central, peripheral, and cardiopulmonary information to produce postganglionic cardiac sympathetic inputs. Pathological anatomical and structural remodeling occurs within the neurons of the stellate ganglion (SG) in the setting of heart failure. A large proportion of SG neurons function as interneurons whose networking capabilities are largely unknown. Current therapies are limited to targeting sympathetic activity at the cardiac level or surgical interventions such as stellectomy, to treat heart failure. Future therapies that target the stellate ganglion will require understanding of their networking capabilities to modify any pathological remodeling. We observe SG networking by examining cofluctuation and specificity of SG networked activity to cardiac cycle phases. We investigate network processing of cardiopulmonary transduction by SG neuronal populations in porcine with chronic pacing-induced heart failure and control subjects during extended in-vivo extracellular microelectrode recordings. We find that information processing and cardiac control in chronic heart failure by the SG, relative to controls, exhibits: i) more frequent, short-lived, high magnitude cofluctuations, ii) greater variation in neural specificity to cardiac cycles, and iii) neural network activity and cardiac control linkage that depends on disease state and cofluctuation magnitude.
Competing Interest Statement
University of California, Los Angeles has patents relating to cardiac neural diagnostics and therapeutics. Dr. Ajijola is a co-founder of NeuCures, Inc. The remaining authors have no additional disclosures to report.
Footnotes
We thank the Reviewing Editor, Senior Editor, and Reviewers for the constructive feedback and suggestions to improve the quality of our manuscript. We have updated our manuscript with the essential and minor revisions requested to the best of our ability and further acknowledged the limitations of the manuscript. In this document, editors and reviewers can see our point by point responses (in blue) and relevant changes in the manuscript with page and line numbers (in red). Summary of Revisions: -Abstract and conclusions have been completely revised. -Mathematical definition figures have been split and captioned in more details -Sections with mathematical explanations have been moved to supplementary material. -Clarifications on the points asked by the reviewers have been added to the manuscript. -Mean values for event rates for control animals and animals with heart failure have been added to the results section.
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