Atrial Rotor Modulation by Localized Dofetilide Application: An In Silico Study

Abstract

The rotor ablation has gained favor in recent years to treat chronic atrial fibrillation (CAF). However, it may cause complications in patients and the results remain suboptimal. Besides, antiarrhythmic drugs for the management of AF are not sufficiently effective and can cause significant cardiac and extracardiac side effects. To reduce the risk and increase the effectiveness, a rotor modulation via the localized release of dofetilide is proposed through an in silico study. A computational model of two-dimensional atrial tissue was implemented using human cell model under CAF conditions. Dofetilide was modeled blocking the ionic currents IKr and IKACh using Hill's equation. A CAF episode, sustained by a rotor, was simulated. Different concentrations of dofetilide were applied in specific distributions based on the rotor tip location, detected by phase map analysis. Non-localized application of dofetilide resulted in the benefit of CAF progression. In contrast, localized dofetilide liberation terminated the CAF episode. These results could have therapeutic implications in novel treatments of CAF.

Cytotoxicity and Genotoxicity of Azobenzene-Based Polymeric Nanocarriers for Phototriggered Drug Release and Biomedical Applications

“…An amount of 0.16 mg/mL PPNP biocompatible concentration encapsulated 19.38 + 0.07 and 57.52 ± 0.09 μM, and photoreleased 98.71 and 97.12% of the Nile red and dofetilide hydrophobic drugs, respectively ( Figure 7 and Table 5 ), upon UV irradiation exposure ( Figure 7 (Cb,E)) by azobenzene-based PPNP trans–cis photoisomerization ( Figure 7 D). The delivered dofetilide antiarrhythmic drug depicted a therapeutic concentration with release-accelerated kinetics for possible atrial fibrillation treatment, as established in a previously reported work (5 μM of dofetilide) [ 41 ]. Then, lower PPNP concentrations were safe and valuable for biomedical applications such as drug delivery, intracellular diagnosis, photodynamic therapy, and theragnosis, among others.…”