Antiarrhythmic properties of a new Suphan-based combined preparation and their possible mechanism of realisation

Abstract

Considerable potentiation of antiarrhythmic and antifibrilation effects of two cardiotonic agents, Suphan and the Na-channel blocker L1, was found in the model experiments in rive with early occlusion and reperfusion arrhythmias. Suphan in combination with L1 inhibited the rise of intraceUular Ca 2+ (by about 70%) in isolated cardiomyocytes incubated under hypoxie conditions. Key words: hypoxia; sodium channel blockers; antiarrhythmic drugs; Ca-exchange; cardiomyocytesCombined action of antiarrhythmic agents in the treatment of cardiac antiarrhythmJa is not adequately investigated. When applied together, some antiarrhythmics, for example, tertiary derivative of Ajmaline (N-propylajmaline-bromide) and local anesthetic Trimecainum in combination with Ethmosine and Ethacisine (all named as Methacisine) potentiate therapeutic effects of each other [1,5]. Combined usage of antiarrhythmic agents with different mechanisms of action allows one to reduce substantially cardiotoxicity and the probability of adverse effects.In this respect, suphan and L-1 (both preparations were synthesised in Russia) seem to be of particular interest. Suphan, di-potassium salt of Nsuccinyl-dl-tryptophan, is a nonglycoside cardiotonic with antianginal and antihypoxia activities. Its antiarrhythmic effect is due predominantly to its action on Ca 2+ exchange in cardiomyocytes [2]. L-l, dimethyl-aminoethyl ether of para-butyl-aminobenzol acid, is a Na-channel blocker by mechanism of action, i.e., it belongs to IB class of antiarrhythmic drugs [8]. MATERIALS AND METHODSAntiarrhythmic activity of the agents was assessed in model experiments with early occlusion and reperfusion arrhythmias on anesthetized eats in rive in complete accordance with the methodical recommendations for experimental (pharmacological) investigation of preparations proposed for clinical trial as agents for cardiac arrhythmia treatment or prevention.The procedures of isolating eardiomyocytes from the left ventricle, then loading with Fura 2-AM, and fluorescence recording were described previously [4]. Intracellular Ca 2 § content was calculated from the following formula: