RSS-Feed abonnieren
DOI: 10.1055/s-0038-1634330
Computational Integrative Physiology: At the Convergence of the Life and Computational Sciences
Publikationsverlauf
Publikationsdatum:
08. Februar 2018 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035037/200302/lookinside/thumbnails/10-1055-s-0038-1634330-1.jpg)
Summary
Objective: In this paper we outline how Computational Integrative Physiology (CIP) can help unravel the mechanisms of normal and pathological biological processes. Our objective is to illustrate how CIP is firmly grounded on the life and computational sciences.
Method: After describing a general theoretical framework for CIP, we will center our discussion on cardiac rhythmic disorders with a particular focus on the Long QT syndrome that will serve as a case example. Within this context, we will describe multi-scale processes in biological, medical and in general mathematical terms, starting from the control of gene expression to the electrical activity of the entire heart. We will therefore proceed from the smaller microscopic scales to the larger macroscopic ones. In doing so, we will illustrate, at least in a qualitative sense, how CIP can be accomplished by showing some of the relations that can exist between mathematical variables characterizing models of different space-scales.
Conclusion: We will conclude by putting forth how CIP and the related fields of bioinformatics and medical informatics are necessary to derive meaningful knowledge from the huge and exponentially growing biological and medical data.
-
References
- 1 Reiss T. Drug discovery of the future: the implications of the human genome project. Trends Biotechnol 2001; 19: 496-9.
- 2 Priori SG. et al. Genetic and molecular basis of cardiac arrhythmias: Impact on clinical management. Part I and II. Circulation 1999; 99: 518-28.
- 3 Romano C, Gemme G, Pongiglione R. Aritmie cardiache rare dell’età pediatrica. Clin Pediatr 1963; 45: 658-83.
- 4 Jervell A, Lange-Nielsen F. Congenital deaf-mutism, functional heart disease with prolongation of the Q-T interval and sudden death. Am Heart J 1957; 54: 59-68.
- 5 Egger LA, Park H, Inouye M. Signal transduction via the hystidyl-aspartyl phosphorelay. Genes Cells 1997; 2: 167-184.
- 6 Endy D, Kong D, Yin J. Intracellular kinetics of a growing virus: a genetically structured simulation for bacteriophage 7. Biotechnol Bioeng 1997; 55: 375-89.
- 7 Alberts B, Watson JD, Bray D. editors. Molecular Biology of The Cell. 3rd ed. Garland Publishing, Inc.; 1994
- 8 Gulrajani RM. Models of electrical activity of the heart and computer simulation of the electrocardiogram. CRC Crit Rev Biomed Eng 1988; 16 (Suppl. 01) 1-66.
- 9 Hodgkin AL, Huxley AF. A quantitative description of membrane current and its application to conduction and excitation in nerve. J Physiol 1952; 117: 500-44.
- 10 Beeler GV, Reuter H. Reconstruction of the action potential of ventricular myocardial fibres. J Physiol 1977; 268: 177-210.
- 11 DiFrancesco D, Noble D. A model of cardiac electrical activity incorporating ionic pumps and concentration changes. Phil Trans R Soc Lond 1985; B 307: 353-98.
- 12 Luo CH, Rudy Y. A dynamic model of the cardiac ventricular action potential, I: simulation of ionic currents and concentration changes. Circ Res 1994; 74: 1071-86.
- 13 Luo CH, Rudy Y. A dynamic model of the cardiac ventricular action potential, II: simulation of ionic currents and concentration changes. Circ Res 1994; 74: 1097-113.
- 14 Priori SG. et al. Genetic and molecular basis of cardiac arrhythmias: Impact on clinical management. Part III. Circulation 1999; 99: 674-81.
- 15 Bonneau R. et al. Functional inferences from blind ab initio protein structure predictions. J Struct Biol, 2001; 134: 186-90.
- 16 Moe GK, Rheinbolt WC, Albiscov JA. A computer model of atrial fibrillation. Am Heart J 1964; 67: 200.
- 17 Van Capelle FJL, Durrer D. Computer simulation of arrhythmias in a network of coupled excitable elements. Circ Res 1980; 47: 454-66.
- 18 Aoki M, Okamoto Y, Musha T, Harumi K. Three-dimensional simulation of the ventricular depolarization and repolarization processes and body surface potentials: normal heart and bundle branch block. IEEE Trans Biomed Eng 1987; 34 (Suppl. 06) 454-62.
- 19 Muller-Borer BJ, Erdman DJ, Buchanan JW. Electrical Coupling and Impulse Propagation in Anatomically Modeled Ventricular Tissue. IEEE Trans Biomed Eng 1994; 41 (Suppl. 05) 445-54.
- 20 Siregar P, Sinteff JP, Julen N, Le Beux P. An interactive 3D anisotropic cellular automata model of the heart. Comput Biomed Res 1998; 31: 323-47.
- 21 Aliev RR, Panfilov AV. Modeling of heart excitation patterns caused by local inhomogeneities. J Theor Biol 1996; 181: 33-40.
- 22 Biktashev VN, Holden AV. Reentrant arrhythmias and their control in models of mammalian cardiac tissue. J Electrocardiol 1999; 32: 76-83.
- 23 Keener JP, Bogar K. A numerical solution of the bidomain equations in cardiac tissue. CHAOS 1998; 8: 234-41.
- 24 Shaw RM, Rudy Y. Ionic mechanisms of propagation in cardiac tissue: roles of sodium and L-Type calcium currents during reduced excitability and decreased gap junction coupling. Circ Res 1997; 81: 727-41.
- 25 Joyner RW. et al. Modulating L-Type calcium current affects discontinuous cardiac action potential conduction. Biophys J 1996; 71: 237-47.
- 26 Fast VG, Kleber AG. Cardiac tissue geometry as a determinant of unidirectional conduction block: assessement of microscopic excitation spread by optical mapping in patterned cell cultures and in a computer model. Cardiovasc Res. 1995; 29: 697-707.
- 27 Spach MS, Kootsey JM. Relating the sodium current and conductance to the shape of trans-membrane and extracellular potentials by simulation:effect of propagation boundaries. IEEE Trans Biomed Eng 1985; 32: 743-55.
- 28 Kleber AG, Riegger CB, Janse MJ. Electrical uncoupling and increase of extracellular resistance after induction of ischemia in isolated, arterially perfused rabit papillary muscle. Circ Res 1987; 61: 271-9.
- 29 Riegger CB, Alperovitch G, Kleber AG. Effect on oxygen withdrawal on active and passive electrical porperties of arterailly perfused rabbit ventricular muscle. Circ Res 1989; 64: 532-41.
- 30 Lory P. et al. Du clonage des canaux calciques de type T à l’étude de leurs rôles physiologiques. J Physiol. 2002; 540 Pt 1 3-14.