Effects of Spatial Distributions of Biological Pacemaker Cells on the Pacemaking Ability of Cardiac Tissue

The biological pacemaker was a promising therapy for cardiac diseases such as sick sinus syndrome and atrioventricular block. A lot of experiments showed that pacemaker cells can be transformed from non-rhythmic cardiac cells or stem cells by gene therapy. However, at the tissue level, the electrophysiological properties between rhythmic and non-rhythmic regions are different. For example, the expression of connexin (such as Cx43) reduced in the induced-pacemaker cells which means that the pacemaker cells may have a less electrical coupling with adjacent cells. In addition, some researches indicated that the spatial distribution of pacemaker cells influenced the excitability of cardiac tissue. To the best of our knowledge, it is still unclear how the spatial distribution of bio-pacemaker cells affects the pacemaking behaviour in biological pacemaker tissue. In this study, we constructed a series of two-dimensional pacemaker-ventricle models containing different distributions of pacemaker cells to investigate the effect of spatial distribution on the pacemaking behaviour. Three kinds of models were designed in our simulations: (1) Tight model; (2) Embedded model; (3) Electrically isolated model. The pacemaking ability of cardiac tissue was measured by the least ratio of pacemaker cells needed to drive the whole tissue. Simulation results showed that electrically isolated model was the optimal model as it showed the best pacemaking ability among these three models. This study may guide the clinical use of biopacemaker.