Both transmural dispersion of repolarization and of refractoriness are poor predictors of arrhythmogenicity： a role for iCEB （QT/QRS）？

We read the original article by Nuis, et al. and the reply by Dogan, et al. with great interest. Nuis, et al. examined whether transcatheter aortic valve implantation （TAVI） in patients suffering from severe aortic stenosis led to changes in corrected QT dispersion （cQTD）, previously used to predict arrhythmic risk. Dogan, et al. proposed that a different marker, transmural dispersion of repolariza- tion （TDR）, has better accuracy in risk prediction.

Carvedilol suppresses ventricular arrhythmia in a pressure over-load rabbit model through relieving transmural dispersion of repolarization with long-term administration

Objective： To investigate the effects of carvedilol （CVD） on transmural dispersion of repolarization（TDR） and arrhythmia in pressure over-load rabbits. Methods： Left ventricular hypertrophied（LVH） rabbit models were established by pressure over-load; All animal models were assigned into CVD group or LVH group randomly. The action potentials of endocardium, cpicardium and transmural ECG of arterially perfused left ventricular preparations were recorded concurrently. Action potential duration （APD）, TDR, ventricular arrhythmia and ultrasonic parameters, ratio of LVM to body weight （LVMI） were compared correspondingly. The stable plasma concentration of carvedilol in CVD group was detected by HPLC. APD, TDR and arrhythmia of LVH models were compared just preor post-perfusion with stable concentration of CVD. Results： In Contrast with values in LVH group, LVEFof CVD group were significantly elevated while the LVMI was remarkably reduced, TDRs were significantly shortened, and ratio of ventricular arrhythmia was lowered remarkably. No significant difference of APD, TDR and ratio of arrhythmia was found preor post-perfusion at stable plasma concentration of CVD. Conclusion： CVD can ameliorate the structure and function of pressure over-load ventricles; CVD contributes to the improvement of ventricular arrhythmia associated with its long-term effect on APD,TDR shortening ,whereas has nothing to do with its transient function on ionic channel blockade

A step forward parameter for the effects of transcatheter aortic valve implantation： transmural dispersion of repolarization

We read the article ＂Effect of transcatheter aortic valve implantation on QT dispersion in patients with aortic stenosis＂ by Erkan, et al. with great interest. In this study, they investigated the effect of transcatheter aortie valve implantation （TAVI） on QT dispersion （QTd） in patients with symptomatic severe aortic stenosis.

Experimental Study of the Effect of Autonomic Nervous System on the Transmural Dispersion of Ventricular Repolarization under Acute Myocardial Ischemia in Vivo

The effect of the autonomic nerves on the transmural dispersion of ventricular repolarization(TDR)under acute myocardial ischemia in intact canine was investigated.Using the monophasic action potential(MAP)recording technique,MAPs of the epicardium(Epi),midmyocardium(Mid)and endocardium(Endo)were recorded simultaneously by specially designed plunge-needle electrodes at the left ventricular free wall under acute myocardial ischemia in 12 open-chest dogs.MAPD 90 and TDR among three myocardial layers as well as the incidence of the early afterdepolarization(EAD)before autonomic nervous stimulation and during autonomic nervous stimulation were compared.It was found that 10 min after acute myocardial ischemia,TDR was increased from 55±8 ms to 86±15 ms during sympathetic stimulation(P<0.01).The TDR(53±9 ms)during parasympathetic stimulation was not significantly different from that of the control(55±8 ms)(P>0.05).The EAD was elicited in the Mid of 2 dogs(16%)10 min after acute myocardial ischemia,but the EAD were elicited in the Mid of 7 dogs(58%)during sympathetic stimulation(P<0.01).It was concluded that:(1)Sympathetic stimulation can increase the transmural dispersion of repolari-zation and induce early afterdepolarizations in the Mid under acute myocardial ischemia,which provide the opportunity for the ventricular arrhythmia developing;(2)Parasympathetic stimulation has no significant effect on the transmural dispersion of repolarization under myocardial ischemia.

Effect of Autonomic Nervous System on the Transmural Dispersion of Ventricular Repolarization in Intact Canine

The effect of the autonomic nerves on the transmural dispersion of ventricular repolarization in intact canine was investigated. By using the monophasic action potential (MAP) recording technique, monophasic action potentials (MAPs) of the epicardium (Epi), midmyocardium (Mid) and endocardium (Endo) were recorded simultaneously by specially designed plunge needle electrodes at the left ventricular free wall in 12 open chest dogs. MAPD 90 and transmural dispersion of repolarization among three myocardial layers as well as the incidence of the EAD before autonomic nervous stimulation and during autonomic nervous stimulation were compared. The results showed that the MAPD 90 of Epi, Mid and Endo before autonomic nervous stimulation were 278±11 ms, 316±16 ms and 270±12 ms respectively, the MAPD 90 of Mid was significantly longer than that of Epi or Endo ( P <0.01). MAPD 90 of Epi, Mid and Endo were shortened by 19±4 ms, 45±6 ms, 18±3 ms respectively during sympathetic stimulation. Compared with that of the control, the transmural dispersion of repolarization during sympathetic stimulation was shortened from 44±4 ms to 15±3 ms ( P <0.01), but early afterdepolarizations were elicited in the Mid of 5 dogs (41 %) during sympathetic stimulation. Parasympathetic stimulation did not significantly affect the MAPD 90 in the three layers. It is concluded that there is the transmural dispersion of ventricular repolarization in intact canine. Sympathetic stimulation can reduce transmural dispersion of repolarization, but it can produce early afterdepolarizations in the Mid. Parasympathetic stimulation does not significantly affect the transmural dispersion of ventricular repolarization.

Novel conduction-repolarization indices for the stratification of arrhythmic risk

Sudden cardiac death （SCD） affects approximately 800,000 individuals per annum globally. It is most frequently due to cardiac tachy-arrhythmias, which include mono-morphic or polymorphic ventricular tachycardia （VT）, torsade de pointes and ventricular fibrillation （VF）. Risk stratification for SCD remains a challenging problem in clinical practice.

Effect of Calcium-Channel Antagonist on Repolarization Heterogeneity of Ventricular Myocardium in an in Vitro Rabbit Model of Long QT Syndrome

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 atrioventricular 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 μmol/L） prolonged QT interval 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--0.05μmol/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 syndrome, blockade of calcium-channel with verapmil had no effect on quinidine-induced changes of repolatiation heterogeneity of ventricular myocardium.

Effects of ramipril on ventricular arrhythmia after myocardial infarction in rabbits

BACKGROUND： Ventricular arrhythmia （VA） is one of the most common complications of myocardial infarction （MI）, and ventricular tachycardia and fibrillation are the main causes for sudden cardiac death. This study aimed to explore the effect of ramipril on the occurrence of VA and its mechanism after MI in rabbits. METHODS： Twenty-four New Zealand rabbits purchased from the Wuhan Laboratory Animal Research Center were divided into three groups： sham-operated （SHAM） group （n=8）, MI group （n=8） and MI with ramipril （RAM） group （n=8）. Rabbits in the SHAM group received a median sternotomy without ligation of the left ventricular coronary artery. Rabbits in the MI and RAM groups received a median sternotomy followed by ligation of the left coronary artery. The successful anterior MI was confirmed by elevation of the ST segment with more than 0.2 mV in lead II and II1. After MI, rabbits in the RAM group were fed with intragastric ramipril （1 mg/kg per day ） for 12 weeks. Before and 12 weeks after MI in the three groups, ventricular tachycardia or fibrillation （VT/VF） episodes and MAP in cadiocytes of the epicardium, mid-myocardium and endocardium were recorded by a multichannel physiograph. Student＇s t test and ANOVA were used for statistical analysis. RESULTS： VT/VF episodes were decreased more markedly in the RAM group than in the MI group after 12 weeks （2.6±0.8 vs. 12.±＋2.9, P〈0.05）. Twelve weeks after MI, the duration of repolarization for 90% （APD90） of three-tier ventricular myocytes in the MI group was longer than that before MI （258.2±21.1 vs. 230.1±23.2,278.0±23.8 vs. 245.8±25.4,242.6±22.7 vs. 227.0±21.7, P〈0.05）. However, the APD90 was not significantly different at 12 weeks before and after MI in the RAM group （P〉0.05）. Moreover, the transmural dispersion of repolarization （TDR） was increased more markedly 12 weeks after MI in the MI group than in the SHAM and RAM groups （36.2±10.2 vs. 18.7±6.2, 24.9±8.7, P〈0.05）. But the TDR was not significantly different between the RAM and SHAM groups （18.7±6.2 vs. 24.9±8.7, P〉0.05）. CONCLUSION： Ramipril may reduce the incidence of malignant ventricular arrhythmia via mprovement of transmembrance repolarization heterogeneity after MI.

Changes of Monophasic Action Potential Duration and Effective Refractory Period of Three Layers Myocardium of Canine during Acute Ischemia in Vivo

Summary： The effect of acute ischemia on the electrophysiological characteristics of the three layers myocardium of canine in vivo was investigated. Twelve canines were divided into two groups randomly： acute ischemia （AI） group and sham operation （SO） group. By using the monophasic action potential （MAP） technique, MAP and effective refractory period （ERP） of the three layers myocardium were measured by specially designed plunge needle electrodes and the transmural dispersion of repolarization （TDR） and transmural dispersion of ERP （TDE） were analyzed. The results showed that in the AI group, MAP duration （MAPD） was shortened from 201.67±21.42 ms to 169.50±13.81 ms （P〈0.05）, but ERP prolonged to varying degrees and TDE increased during ischemia. In the SO group, MAPD and ERP did not change almost. Among of the three layers myocardium of canine, MAPD was coincident in two groups. It was concluded that during acute ischemia, MAPD was shortened sharply, but there was no significant difference among of the three layers myocardium. The prolonged ERP was concomitant with increased TDE during acute ischemia, which may play an important role in the occurrence of arrhythmias induced by acute ischemia. These findings may have important implications in arrhythmogenesis.

KN-93, A CaMKⅡ Inhibitor, Suppresses Ventricular Arrhythmia Induced by LQT2 Without Decreasing TDR

Summary： Abnormal enhanced transmural dispersion of repolarization （TDR） plays an important role in the maintaining of the severe ventricular arrhythmias such as torsades de pointes （TDP） which can be induced in long-QT （LQT） syndrome. Taking advantage of an in vitro rabbit model of LQT2, we de- tected the effects of KN-93, a CaM-dependent kinase （CaMK） II inhibitor on repolarization heteroge- neity of ventricular myocardium. Using the monophasic action potential recording technique, the action potentials of epicardium and endocardium were recorded in rabbit cardiac wedge infused with hypo- kalemic, hypomagnesaemic Tyrode＇s solution. At a basic length （BCL） of 2000 ms, LQT2 model was successfully mimicked with the perfusion of 0.5 μmol/L E-4031, QT intervals and the interval from the peak of T wave to the end of T wave （Tp-e） were prolonged, and Tp-e/QT increased. Besides, TDR was increased and the occurrence rate of arrhythmias like EAD, R-on-T extrasystole, and TDP increased under the above condition. Pretreatment with KN-93 （0.5μmol/L） could inhibit EAD, R-on-T extrasys- tole, and TDP induced by E-4031 without affecting QT interval, Tp-e, and Tp-e/QT. This study demon- strated KN-93, a CaMK II inhibitor, can inhibit EADs which are the triggers of TDP, resulting in the suppression of TDP induced by LQT2 without affecting TDR.