Modeling and Analysis of the Intrinsic Cardiac Nervous System in Closed-Loop Cardiovascular Control

The baroreceptor reflex is a multi-input, multi-output physiological control system that regulates short-term blood pressure by modulating nerve activity between the brainstem and the heart. The computational model by Park et al. (2020) is the most recent iteration in our exploration of the system. However, the contributions of "the little brain of the heart", the intrinsic cardiac nervous system (ICN), to local control of the heart and to the integration of sensory information is unknown and has been overlooked in previous models. We have incorporated a high-fidelity representation of the ICN into a model of the baroreceptor reflex based on anatomical, molecular, and physiological evidence. The model consists of (1) differential equations to represent the cardiovascular system, and (2) transfer functions to represent neural control components, connected in a closed-loop control circuit. We use the model to evaluate the impact of alternative ICN network structures on overall cardiovascular control in response to mean arterial pressure and lung tidal volume perturbations. Our results show that the local circuit neurons that integrate sensory information into the ICN strengthen the response of ICN neuron activity, especially at low blood pressures, suggesting that the ICN amplifies the brainstem's response to perturbations.Copyright (c) 2022 The Authors This is an open access article under the CC BY-NC-ND license (https://creativecommons.org/licenses/by-nc-nd/4.0/)