Abstract
Multiscale models of the cardiovascular system can provide new insights into physiological and pathological processes. PyMyoVent is a computer model that bridges from molecular- to organ-level function and which simulates a left ventricle pumping blood through the systemic circulation. Initial work with PyMyoVent focused on the end-systolic pressure volume relationship and ranked potential therapeutic strategies by their impact on contractility. This manuscript extends the PyMyoVent framework by adding closed-loop feedback control of arterial pressure. The control algorithm mimics important features of the physiological baroreflex and was developed as part of a long-term program that focuses on growth and biological remodeling. Inspired by the underlying biology, the reflex algorithm uses an afferent signal derived from arterial pressure to drive a kinetic model that mimics the net result of neural processing in the medulla and cell-level responses to autonomic drive. The kinetic model outputs control signals that are constrained between limits that represent maximum parasympathetic and maximum sympathetic drive and which modulate heart rate, intracellular Ca2+ dynamics, the molecular-level function of both the thick and the thin myofilaments, and vascular tone. Simulations show that the algorithm can regulate mean arterial pressure at user-defined setpoints as well as maintaining arterial pressure when challenged by changes in blood volume and/or valve resistance. The reflex also regulates arterial pressure when cell-level contractility is modulated to mimic the idealized impact of myotropes. These capabilities will be important for future work that uses computer modeling to investigate clinical conditions and treatments.
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Acknowledgements
Supported by NIH HL133359 and HL163977 to KSC and JFW, NIH HL148785 and TR0001998 to KSC, and AHA TP135689 to KSC.
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HS drafted the manuscript, wrote prototype versions of the code, contributed to the PyMyoVent repository and website, and ran prototype simulations. CKM helped develop the model framework. JFW helped develop the model framework and edited the manuscript. KSC planned the overall project, developed the baroreflex algorithm, wrote the final version of the code, ran the final simulations, created the figures, and finalized the manuscript.
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Sharifi, H., Mann, C.K., Wenk, J.F. et al. A multiscale model of the cardiovascular system that regulates arterial pressure via closed loop baroreflex control of chronotropism, cell-level contractility, and vascular tone. Biomech Model Mechanobiol 21, 1903–1917 (2022). https://doi.org/10.1007/s10237-022-01628-8
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DOI: https://doi.org/10.1007/s10237-022-01628-8