Influence of Amiodarone and Dronedarone on the Force-Interval Dependence of Rat Myocardium.

Dina S Kondratieva,Sergey V Popov,Sergey A Afanasiev

doi:10.1155/2018/4737489

Abstract

The antiarrhythmic effect of amiodarone and its analogue dronedarone is caused by their direct actions on several cardiomyocyte sarcolemmal ion currents. However, whether their effects are related to intracellular calcium levels is not exactly known. Ca2+ cycling refers to the release and reuptake of intracellular Ca2+, which induces muscle contraction and relaxation and determines the force-interval dependence. This study aimed to evaluate the influence of amiodarone and dronedarone on the force-interval relationship. Materials and Results. The work was performed on the papillary muscles of the left ventricle of male Wistar rats. Muscle perfusion was performed at 36.5°C with oxygenated Krebs-Henseleit solution with baseline stimulation 0.5 Hz. The postrest test (4-60 s) and the extrasystolic exposure (0.2-1.5 s) were evaluated. Inotropic reaction to the test exposure was evaluated before and after muscle perfusion with solution containing amiodarone (10−6 M) or dronedarone (10−6 M) during 10 min. Amiodarone or dronedarone led to decrease of the amplitude of extrasystolic contractions of the papillary muscles. The amplitude of postextrasystolic contractions after short extrasystolic intervals on the background of the drugs was increased. Amiodarone and dronedarone led to increase of the amplitude of postrest contractions. Conclusions. Dronedarone reduces the excitability of cardiomyocyte sarcolemma to a greater extent than amiodarone. Amiodarone and dronedarone are able to increase postextrasystolic and postrest potentiation. The effect of amiodarone on postextrasystolic and postrest potentiation is more pronounced in comparison with dronedarone.

Highlights

At the present time amiodarone is the most effective antiarrhythmic drug for the treatment of ventricular and supraventricular arrhythmias [1,2,3]
The results of our studies have shown that amiodarone and dronedarone do not affect the parameters of single contraction-relaxation cycle
Dronedarone, as well as amiodarone, decreased contraction amplitude and velocity parameters of contraction and relaxation; at the same time it increased contraction-relaxation cycle period. These data indicated that dronedarone increased the refractory period, based on drug properties

Summary

Introduction

At the present time amiodarone is the most effective antiarrhythmic drug for the treatment of ventricular and supraventricular arrhythmias [1,2,3] It is a class III antiarrhythmic drug whose main effect occurs through the blockade of potassium channels [4]. Application of amiodarone is limited by the possible development of complications [7,8,9] In this connection development of new drugs that are similar to amiodarone but devoid of its side effects comes at an opportune time. We showed that amiodarone is able to increase postrest contraction amplitude of isolated myocardium strips [13] As it is known potentiation effect of postrest contraction is connected to functional activity of the sarcoplasmic reticulum (SR) [14]. Spontaneous release of calcium ions increases transient ion currents which leads

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Conclusion