Abstract:

In spite of the considerable medical and technical progress during the last years, catheter ablation of atrial fibrillation is still challenging. For a successful execution of the ablation and the avoidance of intricacies the catheter must be in contact with the endocardium, which is still difficult to assure with existent techniques. It would be desirable to detect the endocardial catheter contact directly from the signal shape and its properties. In this work, significant signal property changes were detected and investigated, which allow an automatic contact detection. Furthermore, atrial electrograms were simulated and compared with a database of measured and annotated signals. During these simulations, the distance between endocardium and the catheter tip could be chosen discretionary. The simulated signals revealed themselves to be very accurate. Simulations can now be used to analyse intracardiac signals more closely. The exact position of the catheter will hereby always be assured, which is not always granted in clinical practice.

Abstract:

Atrial fibrillation (AF) is a common pathology. AF modifies the electrophysiological properties of cells (remodeling) promoting the occurrence and maintenance of AF.Electrical remodeling includes changes in ICa,L, Ito, IK1 and IK,ACh. These effects were integrated in a human atrial computer model. Gap junction remodeling was considered in the conductivity of the monodomain equation calculating excitation. Specific features were calculated to determine the risk of AF initiation and perpetuation.ERP was reduced from 330ms to 103ms. CV was lowered from 755mm/s to 608mm/s. The WL reduction was even higher (from 249mm to 63mm) leading to a higher probability of occurrence and maintenance of AF. A maximum of 7 spirals waves were initiated leading to a peak in the power spectrum at 10.32Hz.The computer model underlines the relevance of remodeling in AF chronification. The results add to the knowledge of AF maintenance. Our model might prove to be a tool for the development of novel therapeutic strategies.

Abstract:

In silico studies are valuable in order to understand the exact mechanism of antiarrhythmic drugs and to avoid failures of developmental agents caused by unexpected adverse effects or unsatisfying mechanisms of action. In this work, the effect of amiodarone on chronic atrial fibrillation was investigated by means of computer models. The CRN model was used and was adjusted in order to fit the electrophysiologic characteristics of chronic AF accurately.Amiodarone has a complex profile of action and affects multiple ion channels. These effects can be described as a reduction of the conductivities of the miscellaneous channels and as a variation of the gating kinetics of these channels. As a first method, the altered conductances were adjusted exclusively. The accordant values could be gained from literature. However, literature provided different data, which made a correct assort- ment and integration difficult. Therefore, two different setups were used. Afterwards, simulations in a single cell and in a cell patch, using different pacing frequencies, were accomplished. Then it was obvious that the choice of the data used for the different setups played a crucial role for the final result. Namely, CV, ERP, WL and APD were affected. While the first setup showed a moderate APD prolongation, the APD of Setup 2 was comparatively high. But due to a larger reduction of the CV in Setup 2, the WL of Setup 1 remained longer.Following as a second step, altered kinetics, caused by the drug, were integrated into the CRN model. Therefore, voltage clamp protocols were extracted from literature and compared to current- time curves of the CRN model. Then the data was adjusted using an optimization algorithm. Finally, two dimensional simulations in a planar extract of the right atrium were carried out. First of all, atrial fibrillation in remodelled tissue was created. Then, the dominant frequencies and the numbers of rotating waves were analysed. Afterwards, amiodarone treated tissue was used (Setup 1, Setup 2, kinetic setup), atrial fibrillation was initiated and the accordant parameters were analysed, again.Secondly, the different setups were applied to existing AF. The devolution of the subsequent rotating waves was observed carefully and the same quantitative values were evaluated as before. As a result, compared to control case, Setup 1 showed slightly less rotating waves and only little reduction of the dominant frequency after AF initiation. It showed nearly no effect on rotating waves after acute administration and had to be named only slightly effective. The use of Setup 2 and the setup with altered kinetics made AF initiation more difficult. Alongside the clear reduction of the dominant frequencies compared to the control case, less rotating waves could be created and the administration of acute amiodarone on existing AF terminated rotating waves. So these setups were assigned to be very effective.