Résumé
Intracellular Ca2+ and Ca2+-dependent signaling molecule play an essential role in the genesis of long-QT (LQT) syndrome-related ventricular arrhythmias. The effect of calcium-channel antagonist verapamil on repolarization heterogeneity of ventricular myocardium was assessed in an in vitro rabbit model of LQT syndrome. By using the monophasic action potential (MAP) recording technique, MAPs of epicardium, mid-myocardium and endocardium were simultaneously recorded by specially designed plunge-needle electrodes across the left ventricular free wall in rabbit hearts purfused by Langendorff method with standard Tyrode's solution. Bradycardia was induced by com-plete ablation of atrioventrtcular node. A catheter was introduced into the right ventricle to pace at the cycle lengths (CLs) of 1500, 1000, and 500 ms, successively. Quinidine (2 μol/L) prolonged QT in-terval and ventricular MAP duration (MAPD), and increased transmural dispersion of repolarization (TDR) in a reverse rate-dependent fashion in isolated rabbit heart. No polymorphic ventricular tachycardias were induced under this condition. The effective free therapeutic plasma concentrations of verapamil (0.01-0.05 μmol/L) used in this experiment had no effect on quinidine-induced changes of QT interval, MAPD and TDR. This study demonstrated that, in this model of LQT syn- drome, blockade of calcium-channel with verapmil had no effect on quinidine-induced changes of repolatiation heterogeneity of ventricular myocardium.
Résumé
Objective To study the effects of Pinacidil on Ventricular Repolarization in LQT2 Rabbit Heart.Methods 30 New Zealand white rabbits weighted from 2.5~3.0 kg were randomly divided into 3 groups:group A(control),group B(pinacidil),group C(pinacidil + glibenclamide).Left ventricular endocardium and epicardium MAPs and volume-conducted ECGs in isolated Langendorff-perfused rabbit hearts were recorded simultaneously.To induce bradycardia,the AV nodes of rabbit hearts were damaged.EAD and TdP were induced by means of bradycardia in the presence of high concentration of d-sotalol(10-4M).Results In group B,pinacidil(5?mol/L)shortened the APD90 on endocardium from 445.48?54.31ms to 278.87?44.45ms after administration of pinacidil for 5 minutes(P0.05 vs.group A for all).Conclusion Pinacidil can decrease prolonged action potencial duration and TDR induced by bradycardia and high concentration of d-sotalol in rabbit hearts.Also,pinacidil could abolish the EAD and TdP related to delayed repolarization that may provide a novel and useful intervention in the clinical LQTS patients.