Dispersion of ventricular repolarization: Temporal and spatial

Repolarization heterogeneity(RH)is an intrinsic property of ventricular myocardium and the reason for T-wave formation on electrocardiogram(ECG).Exceeding the physiologically based RH level is associated with appearance of life-threatening ventricular arrhythmias and sudden cardiac death.In this regard,an accurate and comprehensive evaluation of the degree of RH parameters is of importance for assessment of heart state and arrhythmic risk.This review is devoted to comprehensive consideration of RH phenomena in terms of electrophysiological processes underlying RH,cardiac electric field formation during ventricular repolarization,as well as clinical significance of RH and its reflection on ECG parameters.The formation of transmural,apicobasal,left-toright and anterior-posterior gradients of action potential durations and end of repolarization times resulting from the heterogenous distribution of repolarizing ion currents and action potential morphology throughout the heart ventricles,and the different sensitivity of myocardial cells in different ventricular regions to the action of pharmacological agents,temperature,frequency of stimulation,etc.,are being discussed.The review is focused on the fact that RH has different aspects–temporal and spatial,global and local;ECG reflection of various RH aspects and their clinical significance are being discussed.Strategies for comprehensive assessment of ventricular RH using different ECG indices reflecting various RH aspects are presented.

Cardiac Electrophysiological Differences Between Kunming and C57BL6/J Mice

Objective To investigate the alterations of cardiac electrophysiological properties and substantial mechanism and find the stable arrhythmia mouse model in Kunming （KM） and C57BL6/J （C57） mice. Methods Electrocardiogram recordings were used to analyze the QT interval in vivo, and mono- phasic action potential of right and left ventricular epicardium was recorded to elicit changes of action potential duration （APD） in conventional and programmed electrical stimulation （PES）. Transient outward potassium current （Its,） was recorded via whole-cell patch-clamp technique in single right and left epicardial myocytes. Results QT interval was prolonged in KM mice relative to C57 mice （62.51±4.47 ms vs. 52.59±4.85 ms, P〈0.05）. The APD at 50% repolarization of the left ventricular epicardium （18.60±0.91 ms vs. 12.90±0.35 ms）, and APDs at 50% （17.31±6.05 ms vs. 12.00±3.24 ms） and 70% repolarization （36.13±5.32 ms vs. 2 1.95±8.06 ms） of the right ventricular epicardium in KM mice were significantly pro- longed compared with C57 mice, respectively （all P〈0.05）. KM mice were more sensitive to PES-induced ventricular tachycardia （25%, 3 of 12 hearts）, and especially to Burst-induced ventricular tachycardia （50%, 6 of 12 hearts） compared with C57 mice, which were 20% （2 of 10 hearts） and 30% （3 of 10 hearts） respec- tively. It,, densities both in the left and right ventricular epicardial myocytes from KM mice were significantly decreased compared with C57 mice, respectively （all P〈0.01）. Conclusion Our data showed that KM mice with tile prolonged QT interval and APD are ruiner- abilities to ventricular arrhythmia, which are attributed to lower Ito densities in ventricular myocytes ob- tained from KM mice than that from C57 mice.

CT-1-CP-induced Ventricular Electrical Remodeling in Mice

The chronic effects of carboxyl-terminal polypeptide of Cardiotrophin-1（CT-1-CP） on ventricular electrical remodeling were investigated. CT-1-CP, which contains 16 amino acids in sequence of the C-terminal of Cardiotrophin-1, was selected and synthesized, and then administered to Kunming mice（aged 5 weeks） by intraperitoneal injection（500 ng·g^-1·day^-1）（4 groups, n=10 and female： male=1：1 in each group） for 1, 2, 3 and 4 weeks, respectively. The control group（n=10, female：male=1：1） was injected by physiological saline for 4 weeks. The epicardial monophasic action potential（MAP） was recorded by using a contact-type MAP electrode placed vertically on the left ventricular（LV） epicardium surface, and the electrocardiogram（ECG） signal in lead Ⅱ was monitored synchronously. ECG intervals（RR, PR, QRS and QT） and the amplitude of MAP（Am）, the maximum upstroke velocity（Vmax）, as well as action potential durations（APDs） at different repolarization levels（APD30, APD50, APD70, and APD90） of MAP were determined and analyzed in detail. There were no significant differences in RR and P intervals between CT-1-CP-treated groups and control group, but the PR segment and the QRS complex were greater in the former than in the latter（F=2.681 and 5.462 respectively, P〈0.05）. Though QT interval and the corrected QT interval（QTc） were shorter in CT-1-CP-treated groups than in control group, the QT dispersion（QTd） of them was greater in the latter than in the former（F=3.090, P〈0.05） and increased with the time. The ECG monitoring synchronously with the MAP showed that the compression of MAP electrode on the left ventricular epicardium induced performance similar to myocardium ischemia. As compared with those before chest-opening, the PR segment and QT intervals remained basically unchanged in control group, but prolonged significantly in all CT-1-CP-treated groups and the prolongation of QT intervals increased gradually along with the time of exposure to CT-1-CP. The QRS complex had no significant change in control group, one-week and three-week CT-1-CP-treated groups, but prolonged significantly in two-week and four-week CT-1-CP-treated groups. Interestingly, the QTd after chest-opening was significantly greater than that before chest-opening in control group（t=5.242, P〈0.01）, but decreased along with the time in CT-1-CP-treated groups. The mean MAP amplitude, Vmax and APD were greater in CT-1-CP-treated groups than those in control group, and became more obvious along with the time. The APD in four CT-1-CP-treat groups was prolonged mainly in middle to final repolarization phase. The difference among these groups became significant in middle phase（APD50）（F=6.076, P〈0.01） and increased furthermore in late and final phases（APD70： F=10.054; APD90： F=18.691, P〈0.01） along with the time of injection of CT-1-CP. The chronic action of CT-1-CP might induce the adapting alteration in cardiac conductivity and ventricular repolarization. The amplitude and the Vmax of the anterior LV epicardial MAP increased obviously, and the APD prolonged mainly in late and final phase of repolarization.

Effect and mechanism of dexmedetomidine on ischemic arrhythmia

Objective:To explore the antiarrhythmic effect and mechanism of dexmedetomidine,a myocardialα2 receptor agonist in vitro.Methods:Fifty Wistar rats were randomly divided into five groups(n=10):sham operation group(Ctl),arrhythmia model group(Model),arrhythmia+dexmedetomidine group(Dex),arrhythmia+yohimbine+dexmedetomidine group(Yoh+Dex),arrhythmia+yohimbine group(Yoh).The Ctl group just thread left anterior descending coronary artery without ligation.Model group recorded 10 minutes of normal ECG,ligated the left anterior descending coronary artery,and continued to record the ECG for 2 hours.Dex group,Yoh+Dex group and Yoh group were ligated left anterior descending coronary artery after administration.Use BL-420E system to record ECG;Curtis and Walker arrhythmia scores were used to analyze the severity of arrhythmia;perform survival analysis according to the life span of each group of rats;after 21 days of modeling,measure the area of myocardial infarction by TTC staining.The pH value of extracellular fluid was decreased to simulate myocardial ischemia.Patch clamp technique was used to detect the action potential duration of myocardial cells.Results:Compared with the Ctl group,the arrhythmia score and myocardial infarction area in the Model group was increased(P<0.05),the mortality and myocardial infarction area were alsosignificantly reduced(P<0.05).Compared with Model group and Yoh group,the arrhythmia score of Dex group was significantly lower(P<0.001),the mortality and myocardial infarction area were significantly lower(P<0.05);Dexmedetomidine shortened QTc interval(P<0.01),APD50 and APD90(P<0.05).The α_(2) receptor blocker Yohimbine inhibited the effect of dexmedetomidine.Conclusion:Dexmedetomidine affects the action potential repolarization process by stimulating myocardial α_(2) receptors,and prevents ischemia-induced ventricular arrhythmia.

Electrophysiological effects of Chinese medicine Shen song Yang xin （SSYX） on Chinese miniature swine heart and isolated guinea pig ventricular myocytes

Background Shen song Yang xin （SSYX） is a compound of Chinese medicine with the effect of increasing heart rate （HR）. This study aimed to evaluate its electrophysiological properties at heart and cellular levels. Methods The Chinese miniature swines were randomly assigned to two groups, administered with SSYX or placebo for 4 weeks （n=8 per group）. Cardiac electrophysiological study （EPS） was performed before and after drug administration. The guinea pig ventricular myocytes were enzymatically isolated and whole cell voltage-clamp technique was used to evaluate the effect of SSYX on cardiac action potential （AP）. Results SSYX treatment accelerated the HR from （141.8±36.0） beats per minute to （163.0±38.0） beats per minute （P=0.013） without changing the other parameters in surface electrocardiogram. After blockage of the autonomic nervous system with metoprolol and atropin, SSYX had no effect on intrinsic HR （IHR）, but decreased corrected sinus node recovery time （CSNRT） and sinus atrium conducting time （SACT）. Intra cardiac EPS showed that SSYX significantly decreased the A-H and A-V intervals as well as shortened the atrial （A）, atrioventricular node （AVN） and ventricular （V） effective refractory period （ERP）. In isolated guinea pig ventricular myocytes, the most obvious effect of SSYX on action potential was a shortening of the action potential duration （APD） without change in shape of action potential. The shortening rates of APD30, APD50 and APD9o were 19.5%, 17.8% and 15.3%, respectively. The resting potential （Em） and the interval between the end of APD30 and APD90 did not significantly change. Conclusions The present study demonstrates that SSYX increases the HR and enhances the conducting capacity of the heart in the condition of the intact autonomic nervous system. SSYX homogenously decreases the ERP of the heart and shortens the APD of the myocytes, suggesting its antiarrhythmic effect without proarrhythmia.

Cellular mechanism of cardiac alternans： an unresolved chicken or egg problem

T-wave alternans, a specific form of cardiac alternans, has been associated with the increased suscep- tibility to cardiac arrhythmias and sudden cardiac death （SCD）. Plenty of evidence has related cardiac alternans at the tissue level to the instability of voltage kinetics or Ca^2＋ handling dynamics at the cellular level. However, to date, none of the existing experiments could identify the exact cellular mechanism of cardiac alternans due to the bi-directional coupling between voltage kinetics and Ca^2＋ handling dynamics. Either of these systems could be the origin of alternans and the other follows as a secondary change, therefore making the cellular mechanism of alternans a difficult chicken or egg problem. In this context, theoretical analysis combined with experimental techniques provides a possibility to explore this problem. In this review, we will summarize the experimental and theoretical advances in understanding the cellular mechanism of alternans. We focus on the roles of action potential duration （APD） restitution and Ca^2＋ handling dynamics in the genesis of alternans and show how the theoretical analysis combined with experimental techniques has provided us a new insight into the cellular mechanism of alternans. We also discuss the possible reasons of increased propensity for alternans in heart failure （HF） and the new possible therapeutic targets. Finally, according to the level of electrophysiological recording techniques and theoretical strategies, we list some critical experimental or theoretical challenges which may help to determine the origin of alternans and to find more effective therapeutic tar- gets in the future.

Mathematical models of canine right and left atria cardiomyocytes

The aim of this study is to build two mathematical models of canine ionic currents specific to right atria and left atria.The canine left atria mathematical model was firstly modified from the Ramirez-Nattel-Courtemanche(RNC) model using the recently available experimental data of ionic currents and was further developed based on our own experimental data.A model of right atria was then built by considering the differences between right atria and left atria.The two developed models well reproduced the experimental data on action potential morphology,the rate dependence,and action potential duration restitution.They are useful for investigating the mechanisms underlying the het-erogeneity of canine regional action potentials and would help the simulation of whole heart excitation propagation and cardiac arrhythmia in the near future.