Merle Friederike Fenner

PhD student, DVM,

Thesis handed in 10th of May 2019

merle.fenner@sund.ku.dk
ORCID: 0000-0002-5568-7220

merle_fenner@hotmail.com

Research Profile:

Born and raised in Flensburg (Germany) near the German-Danish border, I obtained the veterinary degree (DVM) in 2015 at the University for Veterinary Medicine Hannover, Germany.

After bridging time with a voluntary research project together with Dr. Astrid Bienert-Zeit (Hannover) and Denis Verwilghen (Copenhagen) and a clinical internship at a small animal clinic in Flensburg, I was granted a MARIE SKŁODOWSKA-CURIE ACTIONS Scholarship (Innovative Training Networks (ITN),Call: H2020-MSCA-ITN-2015) at the Department of large Animal Sciences, University of Copenhagen. My PhD project “Establishing a persistent AF horse model for studying the role of K+ channels in the heart” has been part of an EU wide training network, the “AFib-TrainNet” - EU Training Network in Novel Targets and Methods in Atrial Fibrillation.

The aim of my project was to employ the newly established persistent AF model in horses for studying the development of AF over time with focus on the role of K+ channels in horses and especially the effect of pharmacological inhibition of atrial specific potassium currents. Current antiarrhythmic drugs target by inhibiting several ionic currents in the heart, which poses the risk of ventricular pro-arrhythmic effects and other toxicities. This highlights the importance of developing atrial-selective drugs by targeting ion currents predominantly present in the atria - such as IKACh and ISK,Ca.             

We preclinically tested the atrial selective IK,ACh inhibitor XAF-1407 for cardiac and systemic safety as well as its electrophysiological properties and anti-arrhythmic potential in horses with varying duration of AF. We could confirm the atrial-specificity of the IK,ACh blocker XAF-1407and its potential as target for safe treatment of AF. However, with a decreasing efficacy over time, though highly effective in abrogation of AF episodes lasting up to 2 weeks.

In collaboration with experts from the University of Maastricht, we implemented a new protocol for high-density bi-atrial contact mapping in horses. This technique was used in horses for the first time and allowed us to reveal that ISK,Ca inhibition in persistent AF leads to differential electrophysiological effects in the left and right atrium, probably preventing cardioversion success.

In a second collaboration with Maastricht University, implementation of an immunohistochemistry triple-staining method initially developed for human tissue samples, allowed for analysis of equine cardiac tissue specimens for parameters of structural remodelling (fibrosis, fibroblasts and capillary density).

Overall, the synergy between veterinary and human cardiac research was the one common theme in my projects and I hope our groups’ research will continuously gain new insights into cardiac disorders that are of importance for both animal and man in the future. 

Publications:

2018

  • Helena Carstensen, Eva Z. Hesselkilde, Merle Fenner, Ameli V. Loft-Andersen, Mette Flethøj, Jørgen K. Kanters, Stefan M. Sattler, Jacob Tfelt-Hansen, Steen Pehrson, Thomas Jespersen, Rikke Buhl (2018) Time-dependent antiarrhythmic effects of flecainide on induced atrial fibrillation in horses. J Vet Intern Med. 2018; 1-10. https://doi.org/10.1111/jvim.15287
  • Rikke Buhl, Helena Carstensen, Eva Zander Hesselkilde, Bjørg Zinkernagel Klein, Karen Margrethe Hougaard, Kirsten Bomberg Ravn, Ameli Victoria Loft-Andersen, Merle Friederike Fenner, Christian Pipper, Thomas Jespersen (2018) Effect of induced chronic atrial fibrillation on exercise performance in Standardbred trotters. JVIM, (DOI) - 10.1111/jvim.15137
  • M.F. Fenner, D. Verwilghen, N. Townsend, H. Simhofer, J. Schwarzer, D. D. Zani, A. Bienert-Zeit (2018) Paranasal sinus cysts in the horse –Complications related to their presence and surgical treatment in 37 cases. EVJ, (DOI) - 10.1111/evj.12959

2017

  • Hesselkilde, Eva Zander; Carstensen, Helena; Fenner, Merle Friederike (2017) Forskning i hjerteflimmer hos heste - til gavn for både heste og mennesker. Ridehesten, Hippologisk i Avl & Sport, No. 2, 02.2017, p. 62-66 

International proceedings / abstracts 

  • Rikke Buhl, Eva Z. Hesselkilde, Helena Carstensen, Merle F. Fenner, Sarah D. Nissen, Thomas Jespersen (2019) Atrial fibrillation – Translational research perspectives. American College of Veterinary Internal Medicine, Phoenix, Arizona, USA, June 2019
  • Fenner MF, Hesselkilde E, Carstensen H, Nissen S, Lunddahl C, Jensen MA, Loft-Andersen AV, Milnes JT, Sattler SM, Jespersen T, Buhl R (2018) Electrophysiological Properties of a Selective IK,ACh Inhibitor in an Equine, Atrial-Tachypacing-Induced Model of Persistent Atrial Fibrillation. 39th Annual Scientific Sessions HRS 2018, Boston, MA, USA, May 2018
  • Gatta, M.F. Fenner, S. Sattler, U. Schotten, T. Jespersen, S. Verheule, A. Van Hunnik, R. Buhl (2018) Does Size Matter? Characterisation Of A Horse Model Of Chronic Atrial Fibrillation. 39th Annual Scientific Sessions HRS 2018, Boston, MA, USA, May 2018
  • Fenner MF, Hesselkilde E, Carstensen H, Nissen S, Lunddahl C, Jensen MA, Loft-Andersen AV, Milnes JT, Sattler SM, Jespersen T, Buhl R (2018) Electrophysiological Properties of a Selective IK,ACh Inhibitor in an Equine, Atrial-Tachypacing-Induced Model of Persistent Atrial Fibrillation. 14th Annual Congress ECAS 2018, Paris, France, April 2018
  • Fenner, E. Hesselkilde, H. Carstensen, S. Nissen, M. Jensen, C. Lunddahl, J. Milnes, SM. Sattler, T. Jespersen, R. Buhl (2017) Anti-arrhythmic Properties of a Potent, Selective IK,ACh Blocker in an Equine Model of Persistent Atrial Fibrillation. 10th Annual European College of Equine Internal Medicine Congress, Budapest, Hungary, November 2017
  • E Z. Hesselkilde, H. Carstensen, K. Hougaard, K. Bomberg Ravn, M. Fenner, M. Flethøj, D S. Trachsel, T. Jespersen, R. Buhl (2017) Progression of Atrial Fibrillation – A study of atrial remodelling using surface ECG, Tissue Doppler Imaging and Intra Atrial Recordings. 10th Annual European College of Equine Internal Medicine Congress, Budapest, Hungary, November 2017
  • Helena Carstensen, Eva Z. Hesselkilde, Merle Friederike Fenner, Ameli V. Loft-Andersen, Jørgen K. Kanters, Steen Pehrson, Thomas Jespersen, Rikke Buhl (2017) Antiarrhythmic Effects of Flecainide on Experimentally Induced Atrial Fibrillation of Different Duration in Horses. American College of Veterinary Internal Medicine, Washington, USA, June 2017
  • Helena Carstensen, Eva Z. Hesselkilde, Merle Friederike Fenner, Bjørg Z. Klein, Steen Pehrson, Thomas Jespersen, Rikke Buhl (2017) Reduced Exercise Capacity in Horses Due to Atrial Fibrillation. American Colleage of Veterinary Internal Medicine, Washington, USA, June 2017
  • Rikke Buhl, Eva Z. Hesselkilde, Helena Carstensen, Merle Friederike Fenner, Thomas Jespersen, Jacob Tfelt-Hansen, Stefan M. Sattler (2017) Implantable Cardiac Loop Recorders: A Novel Diagnostic Tool for Atrial Fibrillation Detection in Horses. American Colleage of Veterinary Internal Medicine, Washington, USA, June 2017
  • Dagmar S. Trachsel, Helena Carstensen, Eva Z. Hesselkilde, Merle F. Fenner, Rikke Buhl (2017) Effect of Atrial Fibrillation on Exercise Performance in Horses. American Colleage of Veterinary Internal Medicine, Washington, USA, June 2017
  • Fenner M., Verwilghen D., Townsend N., Simhofer H., Schwarzer J., Zani D. D., Bienert-Zeit A. (2017) Review on surgical paranasal sinus cyst treatments in the horse. European College of Veterinary Surgeons, Edinburgh, Scotland, July 2017
  • Fenner M., Verwilghen D., Townsend N., Simhofer H., Schwarzer J., Zani D. D., Bienert-Zeit A. (2017) Paranasal sinus cysts in the horse – Complications related to their presence and surgical treatment - retrospective case series. IGFP Congress, Wiesbaden Niedernhausen, Germany, March 2017
  • Buhl R, Carstensen H, Hesselkilde EZ, Fenner MF, Haugaard MM, Jespersen TJ (2016) Atrial fibrillation – Translational research perspectives. European College of Equine Internal Medicine, Helsinki, Finland, November 2016