Session SA3.3

Development of a Two-Dimensional Model of the Whole Rabbit Heart

J Higham*, H Dobrzynski, MR Boyett, HG Zhang

The University of Manchester
Manchester, UK

Computer modelling of cardiac electrical activity requires detailed descriptions of local cell properties – their action potential (AP) mechanisms, spatial heterogeneities in cellular electrical properties and local intercellular coupling. It also requires an anatomically accurate geometric model of the heart. Over the last decade, we have developed a new family of single cell AP models for all distinctive regions of the rabbit heart including the centre and periphery of the sinoatrial node (SAN) (1), the right atrium (RA) and left atrium (LA) (2), crista terminalis and pectinate muscles (3), Bachmann’s bundle, pulmonary vein and coronary sinus (4), fast and slow pathways of the atrioventricular node (AN and N of the AVN) and His bundle (NH) (5), Purkinje fibers (PF), endocardial (Endo), middle (M) and epicardial (Epi) layers of the left ventricle (LV) (6). These single cell models were based on and validated against experimental data. Using these single cell models, we have developed a two-dimensional (2D) anatomical model for the whole heart conduction system that incorporates regional differences in both cellular electrical properties and intercellular electrical coupling among major distinctive regions of the rabbit heart, including the SAN, atrium muscle, AVN, PF and ventricle. The 2D model of anatomical structure of the heart is based on histologically reconstructed geometry of a single slice of the rabbit heart cut through the long-axis of the heart. The 2D slice was then labelled with different antibodies to characterise different cell types. The geometry was digitized by a high resolution (28 µm) to form regular Cartesian grid of 597 × 587 points. For each point a flag variable identifies whether it belongs to the cell type of the SAN, RA, LA, AVN, PF or ventricle.
The 2D model reproduces the normal activation sequence of the heart with an endogenous SAN driven rate of ~180 beats/min. The activation is first initiated in the centre of the SAN. Once initiated, it propagates towards both atria and then to the AVN. The AVN then transmits the excitation to the PF network and then to excite both the left and right ventricles. The AP conduction velocities range from ~0.1 m/s in the SAN to 1.5 m/s in the PF, which are consistent with experimental data. The whole heart model also produces a pseudo-ECG with intervals (R-R=333 ms, Q-T=214 ms, P-R=85 ms) that fall in the range seen in isolated Langendorff perfused rabbit heart. Simulated effect of acetylcholine (ACh), a neurotransmitter released from vagal nerves upon stimulation, is also consistent with the measurement from Langendorff perfused rabbit heart.

(Abstract Control Number: 100)