Development of a virtual heart - Part l
Seminar Room 1, Newton Institute
Development of a virtual heart requires detailed anatomical models together with a family of action potential models for the different heart regions. In this and the following presentation, we will review progress to develop a virtual rabbit heart at the University of Manchester.
This presentation focuses on the cardiac conduction system, an essential element of a virtual heart. Based on serial sectioning, histology and immunolabelling of marker proteins, we have constructed 3D anatomical models of the rabbit sinoatrial node1 (SAN; pacemaker of heart) and the rabbit atrioventricular node2 (AVN; responsible for action potential conduction from atria to ventricles) as mathematical arrays. The model of the SAN includes both the centre and periphery of the SAN, whereas the model of the AVN includes the transitional zone (fast pathway), the inferior nodal extension (slow pathway) and the penetrating bundle.
Most recently, we have constructed a 3D anatomical model (mathematical array) of the right atrium of the rabbit heart based on high resolution MRI. The model of the right atrium includes 18 segmented objects, including the SAN and AVN and the major atrial muscle bundles, such as the crista terminalis. In 2000 we developed biophysically-detailed models of the action potentials in the centre and periphery of the rabbit SAN.3 More recently, we have developed biophysically-detailed models of the AN, N and NH action potentials (found predominantly in transitional zone, inferior nodal extension and penetrating bundle, respectively) of the rabbit AVN.4 We are using the 3D anatomical models together with the cellular automaton model, the Fitzhugh-Nagumo equations or biophysically-detailed action potential models to compute action potential conduction through the tissue during normal and abnormal activity (such as AVN reentry).
As an alternative strategy, we are using the biophysically-detailed action potential models together with an idealised 1D anatomical model of the AVN to explore the complex electrophysiology of the AVN (such as control of AVN conduction by parasympathetic nervous system).
References (1) H. Dobrzynski et al. Circulation 2005;111:846-54. (2) J. Li et al. Circ Res 2008;102:975-85. (3) H. Zhang et al. Am J Physiol 2000;279:H397-H421. (4) S. Inada et al. Biophys J 2009 (under revision).