Role of L-type Calcium in Modulating Pro-Arrhythmic Effects of Dofetilide in Human

Nejib Zemzemi (1) , Javier Saiz Rodriguez (2) , Rodriguez Blanca (3)

1 CARMEN - Modélisation et calculs pour l'électrophysiologie cardiaque
2 UPV - Universitat Politècnica de València = Universitad Politecnica de Valencia = Polytechnic University of Valencia
3 Computing Science Laboratory - Oxford University

Dofetilide is a class III drug whose use needs to be monitored due to the possible occurrence of Torsades de Pointes (TdP). The mechanisms are unclear but research suggests that both early-afterdepolarizations (EAD) and increased dispersion of action potential duration (APD) might be involved. Importantly, drug-induced TdP is more common in women, possibly due to higher L-type calcium current (ICaL) levels. Our goal is to use numerical simula- tion in order to investigate pro-arrhythmic mechanisms of dofetilide in human by characterizing its effects on APD, APD dispersion and EAD formation for varying doses and ICaL levels.

Domains: Analysis of PDEs [math.AP]; Numerical Analysis [math.NA]

Nejib Zemzemi, Javier Saiz Rodriguez, Rodriguez Blanca. Role of L-type Calcium in Modulating Pro-Arrhythmic Effects of Dofetilide in Human. CinC 2012 - Computing in Cardiology, Sep 2012, Krakow, Poland. pp.861-864. ⟨hal-00764090⟩