Proceedings of The Physiological Society

University of Oxford (2011) Proc Physiol Soc 23, PC129

Poster Communications

Structural and Functional Remodelling Both Contribute to Arrhythmia Substrate in Computational Models of Right Heart Failure

A. P. Benson1, D. Benoist1, S. H. Gilbert1, A. V. Holden1, R. Stones1, E. White1, O. Bernus1

1. Institute of Membrane and Systems Biology, and Multidisciplinary Cardiovascular Research Centre, University of Leeds, Leeds, United Kingdom.


Right heart failure (RHF) can lead to an increased risk of arrhythmias, yet the mechanisms underlying these arrhythmias are less well understood than those in left heart failure (Voelkel et al., 2006). We have developed a computational model of rat RHF, based on experimental measures from monocrotaline (MCT) injected rats, to investigate structural (anatomical) and functional (electrophysiological) mechanisms underlying re-entrant arrhythmias. Ion channel mRNA and monophasic action potential data obtained from both the left (LV) and right (RV) ventricles of control and failing (60 mg/kg MCT) rats (Benoist et al., 2011) were used to scale ion channel conductances in the Pandit et al. (2001) single cell rat model. These were then incorporated into 1D heterogeneous tissue strands, and heterogeneous and anisotropic 3D ventricle models (3 control, 3 RHF). For the ventricle models, anatomy was reconstructed from diffusion tensor magnetic resonance imaging (DT-MRI) at 200 µm resolution (Benson et al., 2011). Model cellular action potential duration increased in RHF, from 36 to 51 ms in LV epicardial cells and from 31 to 78 ms in RV cells, consistent with experimental recordings. In 1D tissue models, RHF increased the refractory period in both the LV and RV, while the mean temporal width of the vulnerable window for unidirectional conduction block increased with RHF in the LV, from 0.8 to 1.4 ms, but decreased in the RV, from 2.2 to 1.7 ms. In the 3D DT-MRI reconstructions, there were no changes to LV structure with MCT, but mean RV wall thickness increased from 1.6 to 2.2 mm and the mean rate of transmural fibre rotation decreased from 148 to 86 °/mm. Following programmed stimulation in the RV wall, we found an increased propensity for sustained arrhythmias in RHF, with the structural and functional changes playing a synergistic role in this increase. In conclusion, using a hierarchy of rat ventricular tissue models we have shown that the initiation and maintenance of arrhythmias in RHF is dependent on both structural and functional remodelling.

Where applicable, experiments conform with Society ethical requirements