Testing of newly synthesized propafenone derivatives antiarrhythmic activity in aconitic model of cardiac arrhythmia in rats

Abstract

By applying of aconitictest in in vivo experiments in rats under deep anesthesia, there was investigated the antiarrhythmic potential of newly synthetized fluorinated derivatives of propafenone. The animals were divided into four experimental groups. The first (aconitine group) was treated with aconitine at a dose of 60 μg/kg, which led to pronounced cardiac rhythm disorder in a short period of time. The appearance of ventricular extrasystole (VES) was taken as a parameter for ascertainment of cardiac rhytm disorder. The remaining three animal groups were taken for testing the potential of propafenone and propafenone fluorinated derivatives to stop the arrhythmia, and which was induced by i.v. aconitine injection (60 μg/kg). Propafenone, as well as 50F derivative, did not convert the disturbed cardiac rhythm (survival of animals was 0%). By applying 5PF derivative in a dose of 6 mg/kg, the animals survived with occasional establishment of sinus rhythm.

Primenom akonitinskog testa, u in vivo eksperimentima na pacovima u dubokoj anesteziji, ispitivan je antiaritmijski potencijal novosintetisanih fluoriranih derivata propafenona. Životinje su podeljene u četiri eksperimentalne grupe. Prva grupa (akonitinska grupa) je tretirana akonitinom u dozi od 60 μg/kg t.m., koja dovodi do vidnog poremećaja srčanog ritma u kratkom vremenskom periodu. Kao parameter za registrovanje poremećaja srčanog ritma uzetaje pojava ventrikularne ekstrasistole (VES). Ostale (tri) eksperimentalne grupe činile su životinje na kojima je ispitivan potencijal propafenona i fluoriranih derivata propafenona da zaustave aritmiju indukovanu i.v. injekcijom akonitina (60 μg/kg t.m.). Propafenon, kao i 50F derivat, nisu uspeli da konvertuju poremećen srčani ritam (preživljavanje životinja je 0 %). Prilikom aplikacije 5PF derivata u dozi od 6 mg/kg t.m. životinje su preživele, uz povremeno uspostavljanje sinusnog ritma.