Antiarrhythmic effect of amiodarone on epinephrine-induced ventricular arrhythmias in rats with experimental hyperglycemia and its combination with hypercholesterolemia
Background: Amiodarone, a class III antiarrhythmic agent, has been shown to be effective against epinephrine-induced ventricular arrhythmias in metabolically neutral animals. However, its effectiveness in models of diabetes mellitus has not yet been studied. The aim of the study:To evaluate the effect of amiodarone on the course of adrenaline-induced ventricular arrhythmias in animals with experimental hyperglycemia (conditionally corresponding to type 1 diabetes) and a combination of hyperglycemia with hypercholesterolemia (conditionally, type 2 diabetes). Materials and methods: This experimental study was conducted on nonlinear male albino Wistar rats weighing 180-220 g. Type 1 diabetes was induced by a single intraperitoneal injection of alloxan at a dose of 135 mg/kg. Type 2 diabetes was reproduced by a single intraperitoneal administration of alloxan at a dose of 135 mg/kg followed by daily intragastric administration of a 1% cholesterol oil solution at a dose of 40 mg/kg/day for 30 days. Ventricular arrhythmias were modelled by a single intravenous injection of adrenaline hydrochloride at a dose of 50 mg/kg on the 30th day of the experiment. Changes in ECG and animal mortality within 30 minutes were assessed, as well as fasting plasma glucose and total cholesterol levels in the groups. Results: Amiodarone hydrochloride (5 mg/kg intravenously, 1-2 minutes prior to inducing epinephrine arrhythmias) did not suppress adrenaline-induced premature ventricular contractions and ventricular tachycardia in rats with type 2 diabetes but did suppress these ventricular arrhythmias in rats with type 1 diabetes, compared to metabolically neutral rats. We hypothesize that the reduction in the antiarrhythmic efficacy of amiodarone may be explained by an increase in its toxicity in the presence of concomitant hypercholesterolemia, as well as by a delayed onset of the antiarrhythmic effect. Conclusion: We are the first to demonstrate a reduction in the antiarrhythmic efficacy of amiodarone in relation to epinephrine-induced ventricular arrhythmias in rats with a combination of hyperglycemia and hypercholesterolemia. Further clinical studies are needed to verify these findings and to determine an effective and safe dose of amiodarone for patients with diabetes mellitus
Kozlov ED, Zorkina AV. Antiarrhythmic effect of amiodarone on epinephrine-induced ventricular arrhythmias in rats with experimental hyperglycemia and its combination with hypercholesterolemia. Research Results in Biomedicine. 2026;12(1):100-111. Russian.
DOI: 10.18413/2658-6533-2026-12-1-0-7
While nobody left any comments to this publication.
You can be first.