Effects Of Mexilitine Combined With Ibutilide On The Electrophysiologic Characteristics Of Canine Left Ventricular Wedge Preperation

Objective：The purpose of this study was to observe the effect of ibutilide on action potentialduration(APD) of endocardium,mid-myocardium and epicardium along with transmuraldispersion of repolarization(TDR) under different basic cycle length(BCL) using canineleft ventricular wedge preperation,and the effects of mexiletine on the electrophysiologicalparameters above when combined with ibutilide.The occurrence of ventricular arrhythmiaswas also observed.And the effects of mexiletine on the safety of appliance of ibutilide.Methods：Canine left ventricular wedge preperations were isolated from the hearts of8healthymongrel dogs.Each wedge preperation received the same treatment:After perfused withnormal Tyrodes’ solution and paced at basic cycle length (BCL) of2000ms for1h to beelectrophysiologically stablized,the wedge preperations were paced at BCL of500ms,667ms,1000ms,2000ms,4000ms, and the transmural ECG and the APD ofepicardium,mid-myocardium and endomyocardium were recorded simutaneously.After theelectrophysiological parameters were recorded,the measurements were repeated after30minutes of appliance of ibutilide Tyrodes’ solution and after30minites of appliance ofibutilide and ibutilide combined with mexiletine,respectively.And transmural dispersion ofrepolarization of wedge preperations were calculated. Spontaneous arrhythmias wasobserved during the entire experiment.Data were expressed as Mean±SD,and wereanalyzed with SPSS16.0software.One-way ANOVA or two-way ANOVA wereapplied;while repeatd measured1-way or2-way ANOVA were applied when analyzingeffects of different perfusate on the electrophysiological parameter.SNK-q test were usedas psot hoc test in the multiple comparative analysis.And t-test or paired t-test were alsoapplied when the difference of two samples were compared.The criterion for statisticalsignificance was P＜0.05.Results：1.The APD of epicardium, mid-myocairidum and endocardium prolonged as pacingfrequency slowed when wedge preperation was canulated with normal Tyrodes’ solution,showing a reverse rate-dependent characteristic, which is more obvious in mid- myocardium. Ibutilide prolonged APD of three layers of myocardium and enhancedreverse rate dependency of myocardial APD, especially that of mid-myocardium.2.Ibutilide presented striking ‘class III effect’ to prolong APD of epicaidium, mid-myocardium and endocardium reverse rate-dependently. The effect to prolong APD onmid-myocardium and its reverse rate dependency of ibutilide is stronger than onepicardium and endocardium, which increased TDR.3.Mexiletine surpressed class III effect of ibutilide on myocardium, especiallymid-myocardium, and its abbreviated reverse rate dependency, and reduced TDR.4.TdP was observed in2wedge preperation when perfusing ibutilide Tyrodes’solution(n=8). And TdP was eliminated after perfusing mexiletine-ibutilide Tyrodes’solution.Conclusion：Mexiletine could inhibit the enhancing effect of ibutilide on APD of three layers ofmyocardium, and surpress class III effect of ibutilide on myocardium, especiallymid-myocardium and the reverse rate dependency of it, so as to reduce TDR. It issuggested that mexiletine might be able to derease substrate for ibutilide to induceventricular arrhythmias and enhance the safety of ibutilide in clinical practice.