Project

In vitro and in vivo models for the development of safe and effective anti-arrhythmic drugs for horses

Code
DOCT/012609
Duration
15 October 2024 → 21 September 2025 (Ongoing)
Doctoral researcher
Research disciplines
  • Medical and health sciences
    • Cardiology
    • Electrophysiology
  • Agricultural and food sciences
    • Veterinary internal medicine and pathophysiology
    • Veterinary physiology, pathophysiology and biochemistry
Keywords
Cardiac arrhythmias in horses Safety pharmacology Patch clamp technique
 
Project description

Cardiac arrhythmias are common in equine athletes and may have fatal consequences. However, anti-arrhythmic drugs for horses are scarce and crucial insights into cardiac electrophysiology are lacking. The currently used anti-arrhythmics are associated with adverse drug effects such as sudden death, and their efficacy is often not evidence-based. In vitro and in vivo models for development of safe and effective anti-arrhythmic drugs are urgently needed. The first objective of this project is to develop an in vitro model for elucidating equine cardiac electrophysiology and evaluating safety pharmacology. On the shelf pharmaceuticals will be evaluated in a heterologous cell model expressing specific equine cardiac ion channels, and through whole-cell patch clamping of equine cardiomyocytes. In addition, a standardised protocol for cryopreservation of cardiomyocytes will be developed in order to create a biobank for in vitro testing. Finally, isolation of cardiomyocytes from endomyocardial biopsies will be investigated, as this may allow electrophysiological studies on tissue of live horses in the future. The second objective is to evaluate the efficacy of existing antiarrhythmic drugs in an in vivo model. The hypothesis is that sotalol, phenytoin and propafenone will decrease atrial fibrillation vulnerability in an experimental equine atrial tachypacing model.