Gee, Michelle M.Lenhoff, Abraham M.Schwaber, James S.Ogunnaike, Babatunde A.Vadigepalli, Rajanikanth2023-04-052023-04-052023-03-21Gee, MM, Lenhoff, AM, Schwaber, JS, Ogunnaike, BA, Vadigepalli, R. Closed-loop modeling of central and intrinsic cardiac nervous system circuits underlying cardiovascular control. AIChE J. 2023; 69( 4):e18033. doi:10.1002/aic.180331547-5905https://udspace.udel.edu/handle/19716/32626This article was originally published in AIChE Journal. The version of record is available at: https://doi.org/10.1002/aic.18033. This work is in memory of Dr. Babatunde A. Ogunnaike, who co-advised Michelle M. Gee and guided the model development and analysis, and represents a milestone in the 30-year collaboration between Dr. Ogunnaike and Drs. Schwaber and Vadigepalli.The baroreflex is a multi-input, multi-output physiological control system that regulates blood pressure by modulating nerve activity between the brainstem and the heart. Existing computational models of the baroreflex do not explicitly incorporate the intrinsic cardiac nervous system (ICN), which mediates central control of heart function. We developed a computational model of closed-loop cardiovascular control by integrating a network representation of the ICN within central control reflex circuits. We examined central and local contributions to the control of heart rate, ventricular functions, and respiratory sinus arrhythmia (RSA). Our simulations match the experimentally observed relationship between RSA and lung tidal volume. Our simulations predicted the relative contributions of the sensory and the motor neuron pathways to the experimentally observed changes in the heart rate. Our closed-loop cardiovascular control model is primed for evaluating bioelectronic interventions to treat heart failure and renormalize cardiovascular physiology.en-USbaroreceptor reflexestimation and control in biological systemsintrinsic cardiac nervous systemphysiological modelingvagus nerve stimulationArticle