Scientific journal
Modern problems of science and education
ISSN 2070-7428
"Перечень" ВАК
ИФ РИНЦ = 1,006

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ANTIARRHYTHMIC ACTIVITY OF AMIODARONE IN SETTINGS OF EXPERIMENTAL DYSLIPIDAEMIA: INFLUENCE OF METABOLIC DISORDERS ON THE DRUG EFFICACY AND TOXICITY

Kozlov E.D. 1 Zorkina A.V. 1
1 National Research Mordovia Ogarev State University
The aim of the research is to evaluate the antiarrhythmic efficacy of amiodarone in models of epinephrine-induced and ischemia-reperfusion ventricular arrhythmias and its toxicity in settings of experimental dyslipidemia. The efficacy of amiodarone was studied in white outbred male laboratory rats. Experimental dyslipidemia was induced through daily administration of a 1% cholesterol and 25000 IU of ergocalciferol for 30 days. Ventricular arrhythmias were modeled using adrenaline injection or 30-minute left coronary artery occlusion followed by 10-minute reperfusion. Amiodarone was administered intravenously at a dose of 5.0 mg/kg-1 1–2 minutes before modeling arrhythmias. Acute toxicity (LD50) of amiodarone was assessed in dyslipidemic mice. In the models of adrenaline- and ischemia-induced arrhythmias, amiodarone significantly reduced the frequency of ventricular tachycardia and ventricular extrasystole in metabolically neutral animals but had reduced efficacy in dyslipidemic rats. Amiodarone was also effective against reperfusion arrhythmias in metabolically neutral, but not dyslipidemic rats. LD50 of amiodarone in dyslipidemic mice was 1,6 times lower than in control ones. The data obtained demonstrate a decrease in the antiarrhythmic efficacy of amiodarone in experimental models of ventricular arrhythmias in settings of lipid metabolism disorders, as well as an increase in its toxicity. The results of the study substantiate the feasibility of preclinical studies on metabolic models to predict the safety and efficacy of drugs and emphasize the need for an individual approach to amiodarone dosing and close monitoring of patients with lipid metabolism disorders.
amiodarone
ventricular arrhythmias
epinephrine-induced arrhythmias
ischemia-reperfusion arrhythmias
antiarrhythmic therapy
cardiac toxicity
dyslipidemia