Modeling of Mechanisms Providing the Overall Control of Human Circulation

Source:
By:Rafik D. Grygoryan

DOI: https://doi.org/10.30564/ahpr.v4i1.4763

Abstract:

Multiple humoral and nervous mechanisms, each influencing the cardiovascular system (CVS) with its specific dynamics and power, had been evolutionarily saved both in animals and in human organisms. Most of such mechanisms are considered to be controllers of CVS’s function, but there is no concept clearly explaining the interaction of global and local controllers in intact human organisms under physiological or pathological conditions. Methodological and ethical constraints create practically insuperable obstacles while experiments on animals mainly concern artificial situations with certain switched-of mechanisms. Currently, mathematical modeling and computer simulations provide the most promising way for expanding and deepening our understanding of regulators’ interactions. As most of CVS’s models describe only partial control mechanisms, a special model (SM) capable of simulating every combination of control mechanisms is encouraged. This paper has three goals: i) to argue the uncial modeling concept and its physiological basis, ii) to describe SM, and iii) to give basic information about SM’s test research. SM describes human hemodynamics, which is under influence of arterial baroreceptor reflexes, peripheral chemoreceptor reflexes, central (CRAS) and local (lRAS) renin-angiotensin systems, local ischemia, and autoregulation of total brain flow. SM, performed in form of special software (SS), is tested under specific endogenous and/or exogenous alterations. The physiologist using SS can easily construct the desirable configuration of regulator mechanisms, their actual state, and scenarios of computer experiments. Tests illustrated the adequateness of SM, are the first step of SM’s research. Nuances of the interaction of modeled regulator mechanisms have to be illustrated in special publications. 

References:

[1] Dampney, R.A., Coleman, M.J., Fontes, M.A., 2002. Central mechanisms underlying short– and long– term regulation of the cardiovascular system. Clinical & Experimental Pharmacology & Physiology. 29, 261-268. [2] Coote, J.H., 2006. Landmarks in understanding the central nervous control of the cardiovascular system. Experimental Physiology. 92, 3-18. [3] Wallin, B.G., Charkoudian, N., 2007. Sympathetic neural control of integrated cardiovascular function: insights from measurement of human sympathetic nerve activity. Muscle Nerve. 36(5), 595-614. [4] Guyton, A.C., Coleman, T.G., Granger, H.J., 1972. Circulation: Overall Regulation. Annual Review of Physiology. 34, 13-46. [5] Cowley, A.W., 1992. Long-term control of arterial blood pressure. Physiological Reviews. 72, 231-300. [6] Fadel, P.J., Ogoh, S., Keller, D.M., et al., 2003. Recent insights into carotid baroreflex function in humans using the variable pressure neck chamber. Experimental Physiology. 88(6), 671-680. [7] De Mello, W.C., Frohlich, E.D., 2011. On the local cardiac renin angiotensin system. Basic and clinical implications. Peptides. 32, 1774-1779. [8] Cowley, A.W., 2008. Renal medullary oxidative stress, pressure-natriuresis, and hypertension. Hypertension. 52, 777-786. [9] Grygoryan, R.D., 2020. Milestones of the modeling of human physiology. Journal of Human Physiology. 2(1), 23-33. DOI: https://doi.org/10.30564/jhp.v2i1.1905 [10] Kokalari, I., 2013. Review on lumped parameter method for modeling the blood flow in systemic arteries. Journal of Biomedical Science and Engineering. 06(01), 92-99. DOI: https://doi.org/10.4236/jbise.2013.61012 [11] Ferguson, D.W., Abboud, F.M., Mark, A.L., 1985. Relative contribution of aortic and carotid baroreflex to heart rate control in man during steady-state and dynamics increases in arterial pressure. Journal of Clinical Investigation. 76, 2265-2274. [12] Grigorian, R.D., 1983. Hemodynamics’ control under postural changes (mathematical modeling and experimental study). Ph.D thesis. Kiev: Institute of Cybernetics. pp. 214. [13] Grygoryan, R.D., 2002. High sustained G-tolerance model development.STCU#P-078 EOARD# 01-8001 Agreement: Final Report. pp. 66. [14] Shimizu, S., Une, D., Kawada, T., et al., 2018. Lumped parameter model for hemodynamic simulation of congenital heart diseases. The Journal of Physiological Sciences. 68, 103-111. DOI: https://doi.org/10.1007/s12576-017-0585-1 [15] Grygoryan, R.D., Lissov, P.N., Aksenova, T.V., et al., 2009. Specialized software-modeling complex “PhysiolResp”. Problems in Programming. 2, 140-150. [16] Grygoryan, R.D., Lissov, P.N., 2004. A software simulator of human cardiovascular system based on its mathematical model. Problems in Programming. 4,100-111. [17] Grygoryan, R.D., 2021. Several Theoretical and Applied Problems of Human Extreme Physiology: Mathematical Modeling. Journal of Human Physiology. 3(02), 57-70. DOI: https://doi.org/10.30564/jhp.v3i2.4175 [18] Grygoryan, R.D., 2011. Energy concept of arterial pressure. Reports of National Academy of Sciences of Ukraine. 7, 148-155. [19] Grygoryan, R.D., 2013. Individual physiological norm: the concept and problems. Reports of National Academy of Sciences of Ukraine. 8, 156-162. [20] Grygoryan, R.D., Lyabach, E.G., 2015. The arterial pressure: a comprehension: Academperiodica, Kiev. [21] Grygoryan, R.D., 2016. The paradigm of “floating” arterial pressure. Palmarium Academic Publishing, Düsseldorf. [22] Grygoryan, R.D., 2017. The optimal circulation: cells contribution to arterial pressure. N.Y.: Nova Science. pp. 287. [23] Grygoryan, R.D., 2019. The Optimal Coexistence of Cells: How Could Human Cells Create The Integrative Physiology. Journal of Human Physiology. 1(01), 8-28. DOI: https://doi.org/10.30564/jhp.v1i1.1386 [24] Grygoryan, R.D., Sagach, V.F., 2018. The concept of physiological super-systems: New stage of integrative physiology. International Journal of Physiology and Pathophysiology. 9(2), 169-180. [25] Dampney, R.A.L., 2017. Resetting of the Baroreflex Control of Sympathetic Vasomotor Activity during Natural Behaviors: Description and Conceptual Model of Central Mechanisms. Frontiers in Neuroscience. 11, 461. DOI: https://doi.org/10.3389/fnins.2017.00461 [26] Dhingra, H., Roongsritong, C., Kurtzman, N.A., 2002. Brain natriuretic peptide: role in cardiovascular and volume homeostasis. Seminars in Nephrology. 22, 423-437. 21 [27] Kang, L., Dunn-Meynell, A.A., Routh, V.H., et al., 2006. Glucokinase is a critical regulator of ventromedial hypothalamic neuronal glucosensing. Diabetes. 55, 412-420. [28] Farag, E., Maheshwari, K., Morgan, J., et al., 2015. An update of the role of renin angiotensin in cardiovascular homeostasis. Anesthesia and Analgesia. 120(2), 275-292. [29] Fauvel, J.P., Cerutti, C., Quelin, P., et al., 2000. Mental stress–induced increase in blood pressure is not related to baroreflex sensitivity in middle–aged healthy men. Hypertension. 35, 887-891. [30] Boscan, P., Pickering, A.E., Paton, J.F., 2002. The nucleus of the solitary tract: an integrating station for nociceptive and cardiorespiratory afferents. Experimental Physiology. 87(2), 259-266. [31] Bruehl, S., Ok, Y.C., 2004. Interactions between the cardiovascular and pain regulatory systems: an updated review of mechanisms and possible alterations in chronic pain. Neuroscience & Biobehavioral Reviews. 28(4), 395-414. [32] Chitravanshi, V.C., Sapru, H.N., 1995. Chemoreceptor-sensitive neurons in commissural subnucleus of nucleus tractus solitarius of the rat. American Journal of Physiology. 268, R851-R858. [33] Burns, K.D., 2000. Angiotensin II and its receptors in the diabetic kidney. American Journal of Kidney Diseases. 36(3), 446-467. [34] Chapleau, M.W., Lu, Y., Abboud, F.M., 2007. Mechanosensitive ion channels in blood pressure-sensing baroreceptor neurons. Current Topics in Membranes. 59, 541-567. [35] Emerling, B.M., Weinberg, F., Snyder, C., et al., 2009. Hypoxic activation of AMPK is dependent on mitochondrial ROS but independent of an increase in AMP/ATP ratio. Free Radical Biology & Medicine. 46(10), 1386-1391. [36] Hardie, D.G., 2008. AMPK: a key regulator of energy balance in the single cell and the whole organism. International Journal of Obesity (Lond). 32(Suppl 4), 7-12. [37] Hardie, D.G., Ashford, M.L., 2014. AMPK: regulating energy balance at the cellular and whole body level. Physiology (Bethesda). 29(2), 99-107. [38] Sparks, M.A., Crowley, S.D., Gurley, S.B., et al., 2014. Classical Renin-Angiotensin system in kidney physiology. Comprehensive Physiology. 4(3), 1201- 1228. DOI: https://doi.org/10.1002/cphy.c130040 [39]Grygoryan, R.D., 2017. Problem-oriented computer simulators for solving theoretical and applied tasks of human physiology. Problems in Programming. 3, 161-171. DOI: https://doi.org/10.15407/pp2017.03.161 [40] Grygoryan, R.D., Aksenova, T.V., Degoda, A.G., 2017. A simulator of mechanisms providing energy balance in human cells. Cybernetics and Computing Technologies. 2, 67-76. DOI: https://doi.org/10.15407/kvt188.02.065 [41] Grygoryan, R.D., Degoda, A.G., Dzhurinsky, Y.A., 2019. A simulator of mechanisms of long-term control of human hemodynamics. Problems of Programming. 4, 111-120. DOI: https://doi.org/10.15407/pp2019.04.111 [42] Grygoryan, R.D., Yurchak, O.I., Degoda, A.G., et al., 2021. Specialized software for simulating the multiple control and modulations of human hemodynamics. Prombles in Programming. 2, 42-53. DOI: https://doi.org/10.15407/pp2021.02.042 [43] Grygoryan, R.D., Yurchak, O.I., Degoda, A.G., et al., 2020. A software technology providing tuning procedures of a quantitative model of human hemodynamics. Problems of Programming. 4, 03-13. DOI: https://doi.org/10.15407/pp2020.04.003