Steering Atrial Lesion Electro-Physiology by Cell Type-Specific Targeting (C17 (P17))

• Subject Area: Cardiology, Angiology ; Anatomy and Physiology
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 422681845

We aim to improve atrial ablation lines. These lines should be as small (narrow) as possible to sustain atrial contractility, mechanically as strong as necessary to avoid rupture, and electrically insulating over long periods of time to reduce the need for re-ablation. Using murine models, we will conduct structure–function studies on atrial lesions in the context of genetic modifications in cardiomyocytes and non-myocytes to explore molecular mechanisms and targets. In a pig model, we will test catheter-based interventions that are compatible with clinical application. In a first-in-human study, we will assess a new Pulsed Field Ablation (PFA) system that has been developed by our collaborators at Stockert GmbH, while sampling biomarkers that may allow improved prediction of ablation success. Using a combination of ex vivo and in vivo assays, we will assess whether PFA can be used for type-preferential targeting, both directly (causing cell death) and indirectly (causing cell uptake of circulating compounds or viral vectors). Our long-term vision is to develop the means for cell type-targeted therapeutic interventions to improve the treatment of atrial rhythm disorders.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1425: Heterocellular Nature of Cardiac Lesions: Identities, Interactions, Implications
• Applicant Institution: Albert-Ludwigs-Universität Freiburg
• Project Heads: Professor Dr. Peter Kohl; Professor Dr. Dirk Westermann