William Hucker:

Modeling the Rabbit AV Junction

 

Long term goal: The long term goal of this project is to construct a 3-D mathematical model of the rabbit AV junction which accurately predicts its macroscopic function. This model will help to understand Atrio-ventricular junctional conduction and arrhythmogenesis.

 

The atrioventricular (AV) node plays several crucial roles in cardiac conduction.  During normal operation, the AV node serves as the electrical conduit between the atria and ventricles and is responsible for the appropriate delay between atrial and ventricular excitation.  In pathological conditions, such as sinoatrial (SA) node failure, the AV node can act as a pacemaker. See movie, which shows AV junctional pacemaker, which kicks in when the SA node fails. [avi]

The AV node can also play a key role in arrhythmias, such as AV nodal reentrant tachycardia (AVNRT).  Because the AV node has such a central role in both the normal and pathologic function of the cardiac conduction system, we are trying to create a 3D mathematical model of its function.

 

 

Fluorescent imaging of AVNRT revealed pattern of conduction during reentry. Upper map shows slow conduction within the posterior AV nodal extension (also known as the slow pathway) and the superior nodal extention (also known as the fast pathway). Lower panel shows fast conduction over the superficial atrial layer.  Note the difference in timing.

 

 

            We obtain functional data to guide our model development using a superfused preparation of the rabbit AV node.  We map the nodal electrical activity using two separate modalities simultaneously: we use a voltage sensitive dye to image the change in voltage that accompanies conduction (see figure, which shows conduction during AVNRT, and we also use standard electrodes placed around the AV nodal region.  This method gives us a comprehensive view of how the AV node functions and provides us with very precise data to guide the development of our model.

Our model will encompass the distribution of various proteins involved in both conduction, as well as the pacemaking activity of the AV node.  We are using immunohistochemistry and confocal microscopy to quantify the distribution of these proteins.  The protein neurofilament acts as a convenient marker of the cardiac conduction system in rabbits.  We use this marker to show us precisely where the conductive tissue is and then we study the distribution of various proteins within this tissue.

                                          

Current state of the project:

            We want to include the neural control of the AV node in our model.  I am currently investigating how the autonomic nervous system affects the AV junctional pacemaker.  We manipulate the autonomic nervous system by applying subthreshold stimulation, which then affects the rate of the junctional pacemaker, and the conduction properties of the AV node.