Experimental Study On The Mechanism About Ventricular Arrhythmia And The Increase Of Transmural Dispersion Of Repolarization

Part one Researches on Potassium Chloride Transmural Recording Electrode of Monophasic Action Potential with Local Administration of AgentsObjective: To design a kind of monophasic action potential(MAP)recording electrode (KCl MAP electrode) which has the capability of agents administration locally, to steadily record the MAP of three myocardial layers synchronously; to probe into the methods of the electrode placement, the stability and duration of MAP recorded by the KCl MAP electrode; to probe into the feasibility of agents administration through the KCl MAP electrode; and to provide an ideal technique for the researches of transmural heterogeneity of repolarization and the mechanism of ventricular arrhythmia of canine in vivo.Methords: The KCl MAP electrode with three pair of electrodes was madeup of 5F arterial sheath and insulated silver thread (0.2mm in diameter), the low melting point agarose gel containing 30% of potassium chloride was immitted into the core of the sheath. Transmural MAP of canine in vivo were recorded with the self-made KCl MAP electrode; the impact of local Isoprenaline on action potential duration(APD) of three layer myocardium, transmural dispersion of repolarization(TDR) and the inducing of ventricular arrhythmia were researched.Results: Transmural MAP could be recorded by the KCl MAP electrode more than 120 minutes with the amplitude of action potential (APA) decreasing gradually but the analysis of the repolarization character not being affected. The APD of mid-myocardial (236.9±3.8ms vs 211.3±3.0ms) and TDR (35.7 ± 4.8 ms vs 24.9 ±3.9 ms) were decreased remarkably by Isoprenaline (10^-5mg/ml), Ventricular arrhythmia induced by early after-depolarization and triggered activity was prone to incurred at mid-myocardial.Conclusion: It is an ideal method for the KCl MAP electrode to be appliedto the researches of transmural repolarization; TDR could be decreased by Isoprenaline and the mechanism of ventricular arrhythmia incurred by Isoprenaline is related to after-depolarization and triggered activity.Part twoElectrophysiological Mechanism of Ventricular Arrhythmia Inducedby Local Isoprenaline in SituObjective To observe the electrophysiological phenomena incurred by theadministration of Isoprenaline(Iso) into canine left anterior ventricular wall in vivo and to probe into the mechanism of ventricular arrhythmia(VA) induced by the inhomogeneity increase of sympathetic nervous tension.Methods The self-made potassium chloride monophasic action potentialrecording electrodes (KCl MAP electrodes ) were pluged into the canine left anterior ventricular wall, where Iso was administered through the KCl MAP electrode to mimic the increase of local sympathetic nervous tension, monophasic action potentials (MAP) of the three layers (endocardium, midmyocardium and epicardium) at left anterior ventricular wall were recorded simultaneously before and after Iso been administered. The monophasic action potential duration (APD), the figure character of MAP , the transmural dispersion of repolarization (TDR) and the activation sequence of transmural anterior ventricular wall were analyzed.Results The APD of all three layers could be decreased directly by Iso withthe TDR decreased remarkablely (31.8 ±2.1ms vs 22.6 ±3.3ms, P<0.05) , a significant increase of TDR (41.0±2.2ms vs 22.6±3.3ms, P<0.05) had been observed when EAD at midmyocardium been induced by Iso. The dependence of EAD on rapid ventricular frequency was observed, and VA could be triggered by consecutive EAD which mainly originated from midmyocardium. Different transmural activation sequence was observed when EAD originated from different layer of left anterior ventricular wall, the sequence was from epicardium to midmyocardium and then to endocardium when VT triggered by EAD originated from midmyocardium while the sequence was from endocardium to midmyocardium and then to epicardium when EAD originated from endocardium.Conclusion The auto-rhythmicity, EAD and TDR could be increasedrelatively by the inhomogeneity increase of Iso, when reentry was easily incurred between the three layer of myocardium, all these might be the electrophysiology bases of VA induced by local Iso.Part threeEffects of Mexiletine on Transmural Dispersion of Repolarization of Left Anterior Ventricular Wall in Canine Model of LQT₃ in Vivo Objective To investigate the changes of action potential duration(APD) and transmural dispersion of repolarization(TDR) in canine model of long-QT syndrome type3(LQT₃) in vivo during bradycardia, to probe into the the impact of the sodium channel block-Mexiletine on this changes, and to provide experimental evidence for the prevention and treatment of ventricular arrhythmia in congenital LQT3.Methords The monophasic action potential(MAP) of endocardium,mid-myocardium and epicardium at the anterior ventricular wall were recorded synchronously in vivo by the self-made electrode, and the body surface electrocardiogram was recorded at the same time, Sea Anemone Toxin (ATX- â…¡) was administered intravenously to mimic LQT3 model, the heart rate was controlled by altering atrium pacing cycle length(PCL) after the sinoatrial node been ablated by 40% formaldehyde.Results The LQT3 model had been made successfully by the intravenousinjection of ATX- â…¡ (3 μg/kg). The TDR had been increased remarkably by the ATX-â…¡ when the PCL was both 500ms and 1000ms (20 ±4 ms vs 41 ± 9ms and 39 ±5ms vs 83 ± 10ms, both P<0.05), but the net increase of TDR(ΔTDR) was more remarkable when the PCL was 1000ms compared with 500ms(44±13ms vs 20 ± 12ms, P<0.05), with the occurrence of early after depolarization(EAD) originated from mid-myocardium and spontaneity ventricular tachycardia. This kind of electrophysiological effect of ATX- â…¡ could be reversed by Mexiletine(20μ g/kg).Conclusion The occurrence of ventricular tachycardia in LQT₃ model isbradycardia dependent, Mexiletine is probably an effective medicine in the prevention and treatment of the sudden cardiac death of congenital LQT₃.