Botulinum Toxin-Chitosan Nanoparticles Prevent Arrhythmia in Experimental Rat Models.

David Sergeevichev,Alexander Chernyavskiy,Elena Chepeleva,Maria Vasilieva,Anna Dokuchaeva,Yanina Rusakova,Artem Strelnikov,Vladislav Fomenko,Sergey Artemenko,Alexander Romanov,Nariman Salakhutdinov

doi:10.3390/md18080410

Abstract

Several experimental studies have recently demonstrated that temporary autonomic block using botulinum toxin (BoNT/A1) might be a novel option for the treatment of atrial fibrillation. However, the assessment of antiarrhythmic properties of BoNT has so far been limited, relying exclusively on vagal stimulation and rapid atrial pacing models. The present study examined the antiarrhythmic effect of specially formulated BoNT/A1-chitosan nanoparticles (BTN) in calcium chloride-, barium chloride- and electrically induced arrhythmia rat models. BTN enhanced the effect of BoNT/A1. Subepicardial injection of BTN resulted in a significant antiarrhythmic effect in investigated rat models. BTN formulation antagonizes arrhythmia induced by the activation of Ca, K and Na channels.

Highlights

Botulinum toxin (BoNT) is a safe and efficient therapeutic means to treat a variety of conditions characterized by the hyperfunction of nerve terminals [1,2]
Rats demonstrating ventricular fibrillation (VF) were included in the statistical analysis of the initial onset time of VF: there were 10 animals in the control, BoNT/A1 (i.v. and subepicardial) and chitosan nanoparticles groups, two animals in the verapamil group and five animals in the BoNT/A1-chitosan nanoparticles (BTN) group (Figure 1)
Several studies have shown that temporary autonomic block using BoNT might be a novel Several option studiesfor have shown that temporary autonomic block

Summary

Introduction

Botulinum toxin (BoNT) is a safe and efficient therapeutic means to treat a variety of conditions characterized by the hyperfunction of nerve terminals [1,2]. There has been a growing interest in BoNT for the treatment of atrial fibrillation (AF). BoNT injected into the sinoatrial fat pad inhibited a decrease in sinus rate in response to vagus nerve stimulation and suggested that BoNT can inhibit ganglionic neurotransmission in the dog heart in situ. Oh et al [4] demonstrated that direct injection of BoNT in epicardial fat pads temporally suppressed AF inducibility in dogs. In the first clinical study of BoNT effects on patients undergoing coronary artery bypass surgery, Pokushalov et al [5] demonstrated that BoNT injection suppresses postoperative atrial fibrillation. Lo et al [6] demonstrated that suppression of the four major atrial ganglionated plexi by BoNT may break the vicious cycle of “AF begets AF” by inhibiting autonomic remodeling, and possibly preventing subsequent progression of AF to more persistent forms. Nazeri et al [7] found that after one week following injection of BoNT into the atrial fat pads of sheep, the vulnerability of atrial tissue to AF induction and the vagal influence on the atrial effective refractory period were reduced compared to baseline levels

Methods

Results

Conclusion