Mapping electrical propagation in the cardiac sinoatrial node: An experimental and computational modelling approach

In mammalian hearts, initiation of the heart beat occurs in the Sinoatrial Node (SAN), commonly referred to as the natural cardiac pacemaker. In this study, experiments were conducted in a few isolated rabbit SAN preparations, excised from live rabbit hearts, to probe propagation parameters of cardiac extracellular potentials from the centre of the SAN to the periphery. Experimental results showed the presence of a region of high resistance surrounding the site of pacemaker activation, possibly shielding the SAN from the more hyperpolarized atrium. Beyond this region, scattered sites of varying velocities of conduction were identified, suggesting the possibility of a mosaic model of distribution of SAN and atrial tissues within the SAN region. Higher velocities were measured towards the Superior Vena Cava and the SAN periphery. Slower propagation was detected towards the Crista Terminalis. This finding suggests the existence of multiple paths of propagation of the cardiac action potential (CAP), with varying properties, emanating from the SAN. The site of initiation of the cardiac wave within the SAN was also found to vary from one beat to the next. Measurements of the propagation of the first ten consecutive beats of each of the independent SAN samples revealed a shift in the site of activation. This finding may suggest the principle of pacemaker oligarchy (i.e. a small number of multiple groups of cells within the SAN controlling activation at every beat). Furthermore, results also revealed an abrupt change in the shape and size of extracellular potentials at different locations, possibly due to abrupt changes in tissue conductance. The study also revealed the spatially-varying tissue conductance at various locations of the examined sample, suggesting the coexistence of both nodal and atrial tissue. Computational monodomain and bidomain models of propagation were also developed to optimise the tissue conductances by comparing experimental propagation times with a modified FitzHugh-Nagumo formulation. The monodomain model was run twice, firstly using a finite difference algorithm, using Matlab as the programming tool, and secondly using a finite element algorithm using COMSOL Multiphysics. Model fits to the data revealed an uneven distribution of velocity of propagation (and therefore of tissue conductance) from the SAN centre to its periphery; however there also appeared to be preferred paths of propagation, namely from the SAN centre to the periphery and to the SVC. The contour of conductances showed generally high values around the SVC and SAN periphery regions. The regions in between showed a spatially-varying distribution of conductances, indicative of a mosaic model of distribution of nodal and atrial cells. The conduction velocity around the SAN centre was fairly modest, indicative of a fairly conductive tissue around the SAN region. Bidomain modelling was used to model the extracellular potential waveshapes. Analysis revealed three types of waveshapes, namely monophasic-positive, monophasic-negative and biphasic waveshapes, similar to the ones obtained experimentally. An investigation into the slope of the extracellular potential wave immediately prior to activation revealed the existence of a gentle positive slope, suggesting slow depolarisation within the wave, possibly indicating the occurrence of pacemaker cells