The integrative model of human physiology connects individual physiological subsystems into a single unit. They are very large (contain thousands of variables) and represent a formalized description of interconnected physiological regulations. The issue of formalization of physiological systems became part of a series of international projects (e.g. the worldwide program "PHYSIOME", or the European program "VIRTUAL PHYSIOLOGICAL HUMAN"). The development of large-scale models of human physiology was facilitated by a new generation (i.e. equation-based) simulation environment, especially by Modelica language. These models can be used to explain the causal relations of the pathogenesis of many diseases, they can be applied in the evaluation of clinical trials and they can also be used in the core of sophisticated medical simulators.
Amosov, N. M., B. L. Palec, B. T. Agapov, I. I. Jermakova, E. G. Ljabach, S. A. Packina, and V. P. Solovjev. 1977. Theoretical Research of Physiological Systems: Matematical Modeling (in Russian). Naukova Dumka.
Atkins, Gordon Leslie. 1969. Multicompartment Models for Biological Systems. Methuen London.
Bassingthwaighte, J. B. 2000. “Strategies for the Physiome Project.” Annals of Biomedical Engineering 28 (8). Springer: 1043–58.
Chen, Jian, Keqin Wu, William A. Pruett, and Robert L. Hester. 2013. “HumMod Browser: An Exploratory Visualization Tool for Model Validation of Whole-Body Physiology Simulation.” In Eurographics Conference on Visualization (EuroVis)(short Paper). researchgate. net. https://www.researchgate.net/profile/Keqin_Wu2/publication/303290077_HumMod_Browser_An_Exploratory_Visualization_Tool_for_Model_Validation_of_Whole-Body_Physiology_Simulation/links/573f6ab108ae298602e8f3cf.pdf.
Coleman, T. G., and R. L. Summers. 1997. “Using Mathematical Models to Better Understand Integrative Physiology.” Journal of Physiology and Biochemistry 53: 45–46.
Fontecave-Jallon, J., and S. R. Thomas. 2015. “Implementation of a Model of Bodily Fluids Regulation.” Acta Biotheoretica 63 (3): 269–82.
Grodins, F. S., J. Buell, and A. J. Bart. 1967. “Mathematical Analysis and Digital Simulation of the Respiratory Control System.” Journal of Applied Physiology 22 (2). DTIC Document: 260–76.
Guyton, A. C. 1981. “The Relationship of Cardiac Output and Arterial Pressure Control.” Circulation 64 (6): 1079–88.
Guyton, A. C., T. G. Coleman, and H. J. Granger. 1972. “Circulation: Overall Regulation.” Annual Review of Physiology 34. annualreviews.org: 13–46.
Guyton, A. C., H. J. Granger, and T. G. Coleman. 1971. “Autoregulation of the Total Systemic Circulation and Its Relation to Control of Cardiac Output and Arterial Pressure.” Circulation Research 28 (January): Suppl 1:93–97.
Guyton, A. C., J. E. Hall, and J. P. Montani. 1988. “Kidney Function and Hypertension.” Acta Physiologica Scandinavica. Supplementum 571: 163–73.
Guyton, A. C., R. D. Manning Jr, R. A. Norman Jr, J. P. Montani, T. E. Lohmeier, and J. E. Hall. 1986. “Current Concepts and Perspectives of Renal Volume Regulation in Relationship to Hypertension.” Journal of Hypertension. Supplement: Official Journal of the International Society of Hypertension 4 (4): S49–56.
Guyton, A. C., and John E. Hall. 2015. Guyton and Hall Textbook of Medical Physiology. Elsevier Health Sciences.
Hester, R., A. Brown, L. Husband, and R. Iliescu. 2011. “Hum-Mod: A Modeling Environment for the Simulation of Integrative Human Physiology.” Frontiers in. journal.frontiersin.org. http://journal.frontiersin.org/article/10.3389/fphys.2011.00012.
Hester, R. L., T. Coleman, and R. Summers. 2008. “A Multilevel Open Source Integrative Model of Human Physiology.” The FASEB Journal 22 (1 Supplement): 756.8–756.8.
Hester, R. L., R. Iliescu, R. Summers, and T. G. Coleman. 2011. “Systems Biology and Integrative Physiological Modelling.” The Journal of Physiology 589 (Pt 5). Wiley Online Library: 1053–60.
Hodgkin, A. L., and A. F. Huxley. 1952. “A Quantitative Description of Membrane Current and Its Application to Conduction and Excitation in Nerve.” The Journal of Physiology 117 (4). ncbi.nlm.nih.gov: 500–544.
Hunter, P. 2016. “The Virtual Physiological Human: The Physiome Project Aims to Develop Reproducible, Multiscale Models for Clinical Practice.” IEEE Pulse 7 (4). ieeexplore. ieee.org: 36–42.
Hunter, P., J. Edmund, J. Crampin, and Poul M. F. Nielsen. 2008. “Bioinformatics, Multiscale Modeling and the IUPS Physiome Project.” Briefings in Bioinformatics 9 (4). Oxford Univ Press: 333–43.
Hunter, P., P. Robbins, and D. Noble. 2002. “The IUPS Human Physiome Project.” Pflugers Archiv: European Journal of Physiology 445 (1). Springer: 1–9.
Hunter, P. J., W. W. Li, A. D. McCulloch, and D. Noble. 2006. “Multiscale Modeling: Physiome Project Standards, Tools, and Databases.” Computer 39 (11). ieeexplore.ieee.org: 48–54.
Ikeda, N., F. M., M. Shirataka, and T. Sato. 1979. “A Model of Overall Regulation of Body Fluids.” Annals of Biomedical Engineering 7 (2): 135–66.
Kofranek, J., M. Matejak, and P. Privitzer. 2011. “Hummod-Large Scale Physiological Models in Modelica.” In Proceedings of the 8th International Modelica Conference; March 20th-22nd; Technical Univeristy; Dresden; Germany, 713–24. Linköping University Electronic Press.
Kofránek, J., M. Mateják, P. Privitzer, M. Tribula, T. Kulhánek, J. Šilar, and R. Pecinovský. 2013. “HumMod-Golem Edition: Large Scale Model of Integrative Physiology for Virtual Patient Simulators.” In Proceedings of the International Conference on Modeling, Simulation and Visualization Methods (MSV), 1. The Steering Committee of The World Congress in Computer Science, Computer Engineering and Applied Computing (WorldComp).
Kofranek, J., and J. Rusz. 2010. “Restoration of Guyton’s Diagram for Regulation of the Circulation as a Basis for Quantitative Physiological Model Development.” Physiological Research / Academia Scientiarum Bohemoslovaca 59 (6). Institute of Physiology: 897.
Kofránek, J., L. D. Anh Vu, H. Snaselova, R. Kerekeš, and T. Velan. 2001. “GOLEM-Multimedia Simulator for Medical Education.” Studies in Health Technology and Informatics, no. 2. IOS Press; 1999: 1042–46.
Kofránek, J., M. Mateják, and P. Privitzer. 2010. “Web Simulator Creation Technology.” MEFANET Report 3: 32–97.
Kohl, P., E. J. Crampin, T. A. Quinn, and D. Noble. 2010. “Systems Biology: An Approach.” Clinical Pharmacology and Therapeutics 88 (1): 25–33.
Kohl, P., and D. Noble. 2009. “Systems Biology and the Virtual Physiological Human.” Molecular Systems Biology 5 (July): 292.
Kulhánek, T., J. Kofránek, and M. Mateják. 2014. “Modeling of Short-Term Mechanism of Arterial Pressure Control in the Cardiovascular System: Object-Oriented and Acausal Approach.” Computers in Biology and Medicine 54 (November): 137–44.
Lerant, A. A., R. L. Hester, T. G. Coleman, W. J. Phillips, J. D. Orledge, and W. B. Murray. 2015. “Preventing and Treating Hypoxia: Using a Physiology Simulator to Demonstrate the Value of Pre-Oxygenation and the Futility of Hyperventilation.” International Journal of Medical Sciences 12 (8). ncbi.nlm.nih.gov: 625–32.
Mangourova, V., J. Ringwood, and B. Van Vliet. 2011. “Graphical Simulation Environments for Modelling and Simulation of Integrative Physiology.” Computer Methods and Programs in Biomedicine 102 (3). Elsevier: 295–304.
Mateják, M.. 2014. “Physiology in Modelica.” MEFANET Journal 2 (1). Facta Medica: 10–14.
Mateják, M. 2015. “Formalization of Integrative Physiology. Charles University in Prague.” Edited by Jirí Kofránek. Ph.D., Charles University. https://github.com/MarekMatejak/dissertation/blob/master/thesis.pdf.
Mateják, M-, F. Ježek, M. Tribula, and J. Kofránek. 2015. “Physiolibrary 2.3-An Intuitive Tool for Integrative Physiology.” IFAC-PapersOnLine 48 (1). Elsevier: 699–700.
Mateják, M., T. Kulhánek, J. Šilar, P. Privitzer, F. Ježek, and J. Kofránek. 2014. “Physiolibrary-Modelica Library for Physiology.” In Proceedings of the 10 Th International Modelica Conference; March 10-12; 2014; Lund; Sweden, 499–505. Linköping University Electronic Press.
Mateják, M., M. Tribula, F. Ježek, and J. Kofranek. 2015. “Free Modelica Library for Chemical and Electrochemical Processes.” In Proceedings of the 11th International Modelica Conference, Versailles, France, September 21-23, 2015, 359–66. Linköping University Electronic Press.
Mateják, M., and J. Kofránek. 2015. “Physiomodel-an Integrative Physiology in Modelica.” And Biology Society (EMBC), 2015 37th …. ieeexplore.ieee.org. http://ieeexplore.ieee.org/abstract/document/7318646/.
McCulloch, Warren S., and Walter Pitts. 1943. “A Logical Calculus of the Ideas Immanent in Nervous Activity.” The Bulletin of Mathematical Biophysics 5 (4). Kluwer Academic Publishers: 115–33.
Milhorn, H. T. 1966. Application of Control Theory to Physiological Systems. W.B. Saunders.
Montani, J. P. and Bruce N. Van Vliet. 2009. “Understanding the Contribution of Guyton’s Large Circulatory Model to Long-Term Control of Arterial Pressure.” Experimental Physiology 94 (4). Wiley Online Library: 382–88.
Montani, J. P., T. H. Adair, R. L. Summers, T. G. Coleman, and A. C. Guyton. 1989. “A Simulation Support System for Solving Large Physiological Models on Microcomputers.” International Journal of Bio-Medical Computing 24 (1): 41–54.
Montani, J. P., H. L. Mizelle, T. H. Adair, and A. C. Guyton. 1989. “Regulation of Cardiac Output during Aldosterone-Induced Hypertension.” Journal of Hypertension. Supplement: Official Journal of the International Society of Hypertension 7 (6): S206–7.
Moss, R., T. Grosse, I. Marchant, N. Lassau, F. Gueyffier, and S. R. Thomas. 2012. “Virtual Patients and Sensitivity Analysis of the Guyton Model of Blood Pressure Regulation: Towards Individualized Models of Whole- Body Physiology.” PLoS Computational Biology 8 (6): e1002571.
Omholt, S. W., and P. J. Hunter. 2016. “The Human Physiome: A Necessary Key for the Creative Destruction of Medicine.” Interface Focus 6 (2). Royal Society: 20160003.
Pitts, W., and W. S. McCulloch. 1947. “How We Know Universals; the Perception of Auditory and Visual Forms.” The Bulletin of Mathematical Biophysics 9 (3). Springer: 127–47.
Potucek, J., M. Hájek, V. Brodan, and E. Kuhn. 1977. “The Method of Estimating Biological System Parameters on Hybrid Computer.” Kybernetika 13 (2). Institute of Information Theory and Automation AS CR: 153–64.
Pruett, W. Andrew, John S. Clemmer, and Robert L. Hester. 2016. “Validation of an Integrative Mathematical Model of Dehydration and Rehydration in Virtual Humans.” Physiological Reports 4 (22). doi: https://doi.org/10.14814/phy2.13015.
Pruett, W., L. Husband, and R. Hester. 2014. “Understanding Variation in Salt Sensitivity in HumMod, a Human Physiological Simulator (857.11).” The FASEB Journal 28 (1 Supplement). http://www.fasebj.org/content/28/1_Supplement/857.11.abstract.
Sheppard, C. W. 1948. “The Theory of the Study of Transfers within a Multi-Compartment System Using Isotopic Tracers.” Journal of Applied Physics 19 (1). AIP: 70–76.
Shim, E. B, Ch. H. Leem, Y. Abe, and A. Noma. 2006. “A New Multi-Scale Simulation Model of the Circulation: From Cells to System.” Philosophical Transactions. Series A, Mathematical, Physical, and Engineering Sciences 364 (1843): 1483–1500.
Summers, R. L., S. Platts, J. G. Myers, and T. G. Coleman. 2010. “Theoretical Analysis of the Mechanisms of a Gender Differentiation in the Propensity for Orthostatic Intolerance after Spaceflight.” Theoretical Biology & Medical Modelling 7 (March): 8.
Thomas, S. R., P. Baconnier, J. Fontecave, J. P. Françoise, F. Guillaud, P. Hannaert, A. Hernández, et al. 2008. “SAPHIR: A Physiome Core Model of Body Fluid Homeostasis and Blood Pressure Regulation.” Philosophical Transactions. Series A, Mathematical, Physical, and Engineering Sciences 366 (1878). rsta.royalsocietypublishing.org: 3175–97.
Von Bertalanffy, L. 1973. General Systems Theory. George Braziller Inc., New York.
White, R. J., and J. C. McPhee. 2007. “The Digital Astronaut: An Integrated Modeling and Database System for Space Biomedical Research and Operations.” Acta Astronautica 60 (4–7). Elsevier: 273–80.
Wu, K., J. Chen, W. A. Pruett, and R. L. Hester. 2013. “Hummod Browser: An Exploratory Visualization Tool for the Analysis of Whole-Body Physiology Simulation Data.” In 2013 IEEE Symposium on Biological Data Visualization (BioVis), 97–104. ieeexplore.ieee.org.
Xu, L., J. Lyle, Y. Wu, Z Pan, M. Zhang, D. H. Laidlaw, R. L. Hester, and J. Chen. 2011. “HumMod Explorer: A Multi-Scale Time-Varying Human Modeling Navigator.” In SIGGRAPH Asia 2011 Posters, 28:1–28:1. SA ’11. New York, NY, USA: ACM.
Zhang, S., W. A. Pruett, and R. Hester. 2015. “Visualization and Classification of Physiological Failure Modes in Ensemble Hemorrhage Simulation.” In SPIE/IS&T Electronic Imaging, 93970O – 93970O – 8. International Society for Optics and Photonics.
