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.

Effects of ramipril on ventricular arrhythmia after myocardial infarction in rabbits

BACKGROUND: V entricular arrhythmia(VA) is one of the most common complications of myocardial infarction(MI), and ventricular tachycardia and fi brillation 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 confi rmed by elevation of the ST segment with more than 0.2 mV in lead II and III. 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 fi brillation(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. 12.4±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 signif icantly 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 signifi cantly 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 improvement of transmembrance repolarization heterogeneity after MI.

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.