Michelle M. Gee (1,2), Abraham M. Lenhoff (1), James S. Schwaber (1,2), Rajanikanth Vadigepalli (1,2) 1 Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, DE 19716 2 Daniel Baugh Institute of Functional Genomics/Computational Biology, Department of Pathology and Genomic Medicine, Thomas Jefferson University, Philadelphia, PA 19107
Poster # 23
The baroreflex is a multi-input, multi-output physiological control system that regulates short-term blood pressure by modulating motor (efferent) and sensory (afferent) vagal nerve activity between the brainstem and the heart. The primary objective of the baroreflex is to maintain near-constant blood pressure while balancing multiple demands for blood flow to different organs, including coping with disturbances such as those caused by respiration or exercise. The baroreflex is regulated by the opposing effects of vagal and sympathetic activity, which decrease and increase heart rate and blood pressure, respectively. The vagus sends inputs to the heart's "little brain", the intrinsic cardiac nervous system (ICN), which receives motor inputs from the vagus to mediate central control of heart function. Following myocardial infarction, neuronal remodeling throughout the ICN, cardiovascular sensory afferents, and brainstem occurs. A hallmark of this remodeling process and of cardiovascular disease is decreased efferent vagal tone, but whether the decrease is due to remodeling in the ICN, afferents, or brainstem is not well understood. We have recently developed a computational model of closed-loop cardiovascular control by integrating a network representation of the ICN with central control reflex circuits using detailed anatomical and functional data. We use the model to analyze different scenarios of central (brainstem) versus peripheral (ICN and afferent) dysfunction that could lead to decreased vagal efferent activity. Our model suggests that afferent dysfunction in the form of baroreflex sensitivity or brainstem remodeling could account for decreased vagal tone following myocardial infarction. These model predictions align with recent experimental observations that afferent remodeling is at least partially responsible for decreased vagal efferent tone following myocardial infarction.
Comments