Summary： To study the effect of of lidocaine and amiodarone on the transmural heterogeneity of ventricular repolarization in isolated rabbit hearts model of sustained global ischemia and to explore the mechanisms und...Summary： To study the effect of of lidocaine and amiodarone on the transmural heterogeneity of ventricular repolarization in isolated rabbit hearts model of sustained global ischemia and to explore the mechanisms underlying the antiarrhythmic activity of lidocaine and amiodarone, rabbits were randomly divided into 4 groups： control group, ischemia group, lidocaine group and amiodarone group. By the monophasic action potential （MAP） recording technique, MAPs of epicardium, midmyocardium and endocardium were simultaneously recorded across the left ventricular free wall in rabbit hearts perfused by low-flow ischemia （2. 5 mL/min） in Langendorff method to study the transmural dispcrsion of repolarization （TDR） and arrhythmic induced by ischemia.Our results showed that TDR of three myocardial layers in ischemia group were significantly lengthened after ischemia. TDR was increased from 17.5±3.9 ms to 31.2±4.6 ms at the time that concided with the onset of sustained ventricle arrhythmic. Amiodarone could decrease TDR, but lidocaine could increase TDR at initial ischemia, and no significant difference was found at other ischemia time points. 5 cases had ventriclar arrhythmia in ischemia group （62. 5%）, but no case in lidocaine group （P〈0.01） and only 1 case in amiodarone group had ventrilar arrhythmia （P〈 0.01）. No significant difference was found between amiodarone group and lidocaine group. It is concluded that TDR of of three myocardial layers increases significantly at ischemia and it is closely associated with development of ventricular arrhythmia, and amiodarone could decrease TDR, but lidocaine could increase TDR at initial ischemia and has no effects at other ischemia time points.展开更多
Objective:To observe effects of hypokalemia on transmural heterogeneity of ventricular repolarization in left ventricular myocardium of rabbit,and explore the role of hypokalemia in malignant ventricular arrhythmia（...Objective:To observe effects of hypokalemia on transmural heterogeneity of ventricular repolarization in left ventricular myocardium of rabbit,and explore the role of hypokalemia in malignant ventricular arrhythmia（MVA）.Methods:A total of 20 rabbits were randomly divided into control group and hypokalemic group.Isolated hearts in the control group were simply perfused with modified Tyrode’s solution,and were perfused with hypokalemic Tyrode’s solution in hypokalemic group.Ventricular fibrillation threshold（VFT）,90%monophasic action potential repolarization duration(APD<sub>90</sub>) of subepicardial,midmyocardial and subendocardial myocardium,transmural dispersion of repolarization（TDR） and Cx43 protein expression in three layers of myocardium were measured in both groups.Results:VFT in the control group and the hypokalemic group were（13.40±2.95） V,and（7.00±1.49） V,respectively.There was a significant difference between two groups（P【0.01）.APD<sub>90</sub> of three myocardial layers in the hypokalemic group were significantly prolonged than those in the control group（/’【0.01）.△APD<sub>90</sub>in the hypokalemic group and the control group were（38.10±10\29） ms and（23.7015.68） ms,and TDR were（52.90<sub>r</sub> 14.55） ms and（36.10±12.44） ms,respectively.△APD<sub>90</sub> and TDR in the hypokalemic group were significantly higher than those in the control group(P【0.05|,and the increase in△APD<sub>90</sub> of midmyocardium was more significant in the hypokalemic group.Cx43 protein expression of all three myocardial layers were decreased significantly in the hypokalemic group（P【0.01）, and△APD<sub>90</sub> was significantly increased {P【0.05).Reduction of Cx43 protein expression was more significant in the midmyocardium.Conclusions:Hypokalemic can increase transmural heterogeneity of Cx43 expression and repolarization in left ventricular myocardium of rabbit,and decrease VFT and can induce MVA more easily.展开更多
Objective: Although after pacing animal and human studies have demonstrated a rate-dependent effect of sotalol on ventricular repolarization, there is little information on the effects of sotalol on ventricular repola...Objective: Although after pacing animal and human studies have demonstrated a rate-dependent effect of sotalol on ventricular repolarization, there is little information on the effects of sotalol on ventricular repolarization during exercise. This study attempted to show the effects of sotalol on ventricular repolarization during physiological exercise. Methods: Thirty-one healthy volunteers (18 males, 13 females) were enrolled in the study. Each performed a maximal treadmill exercise test according to the Bruce protocol after random treatment with sotalol, propranolol and placebo. Results: Sotalol significantly prolonged QTc (corrected QT) and JTc (corrected JT) intervals at rest compared with propranolol (QTc 324.86 ms vs 305.21 ms, P<0.001; JTc 245.04 ms vs 224.17 ms, P<0.001) and placebo (QTc 324.86 ms vs 314.06 ms, P<0.01; JTc 245.04 ms vs. 232.69 ms, P<0.001). The JTc percent reduction increased progressively with each stage of exercise and correlated positively with exercise heart rate (r=0.148, P<0.01). The JTc percent reduction correlation with exercise heart rate did not exist with either propranolol or placebo. Conclusions: These results imply that with sotalol ventricular repolarization is progressively shortened after exercise. Thus the specific class III antiarrhythmic activity of sotalol, present as delay of ventricular repolarization, may be attenuated during exercise. Such findings may imply the need to consider other antiarrythmic therapy during periods of stress-induced tachycardia.展开更多
This study aimed to describe the epidemiology of repolarization dispersion (QT dispersion and Tpeak-Tend dispersion) and further describe their associated clinical correlates among uncontrolled arterial hypertension i...This study aimed to describe the epidemiology of repolarization dispersion (QT dispersion and Tpeak-Tend dispersion) and further describe their associated clinical correlates among uncontrolled arterial hypertension in type-2 Diabetics patient, in western region of the Republic of Macedonia. Abnormal ventricular repolarization is associated with increased cardiovascular risk. Data relating to the frequency of increased repolarization dispersion, among uncontrolled arterial hypertension in type-2 Diabetics patient in western region of the Republic of Macedonia, are scarce. A total of 600 patients were enrolled into this observation study. Study participans were selected among primary care patient, who were receiving ongoing care for diabetes mellitus and hypertension during 1 calendar year. Twelve lead resting electrocardiography, QT, QTc, Tpeak-Tend-intervals and dispersions, were determined manually, and were compared between groups. Patients with uncontrolled BP have greater frequency of: prolonged QTc.max.interval, (61.3% vs.33.6%;p = 0.0005), prolonged Tpeak-Tend interval (65.3% vs. 34.7%;p = 0.005), increased dispersion of QTc. interval (65.9% vs. 34.1%;p = 0.00), increased disperion of Tpeak-Tend interval (65.5% vs. 34.5%;p = 0.002). Females with uncontrolled BP have greater frequency of: increased dispersion of QTc. interval (61.2% vs. 38%;p = 0.02), increased dispersion of Tpeak-Tend interval (63.1% vs. 31.5%;p = 0.008). Hypertensive diabetic patients with uncontrolled BP and abnormal ventricular repolarization have greater BMI (p = 0.000;95%CI 3.849 - 7.871), longer duration of D.M (p = 0.000;95%CI 1.600 - 1.981), longer duration of arterial hypertension (p = 0.000;95%CI 1.468 - 1.850) and less controlled glycemia (p = 0.000;95%CI 1.556 - 3.004). Frequency of increased set of electrophysiological parameters that indicate a prolonged and more heterogeneous repolarization among diabetic patients with uncontrolled BP, is considerable high and seems to be significantly associated with demographic and clinical parameters: gender, BMI, duration of diabetes, duration of BP and glycemic control.展开更多
Malignant cardiac arrhythmias which result in sudden cardiac death may be present in individuals apparently healthy or be associated with other medical conditions. The way to predict their appearance represents a chal...Malignant cardiac arrhythmias which result in sudden cardiac death may be present in individuals apparently healthy or be associated with other medical conditions. The way to predict their appearance represents a challenge for the medical community due to the tragic outcomes in most cases. In the last two decades some ventricular repolarization(VR) markers have been found to be useful to predict malignant cardiac arrhythmias in several clinical conditions. The corrected QT, QT dispersion, Tpeak-Tend, Tpeak-Tend dispersion and Tp-e/QT have been studied and implemented in clinical practice for this purpose. These markers are obtained from 12 lead surface electrocardiogram. In this review we discuss how these markers have demonstrated to be effective to predict malignant arrhythmias in medical conditions such as long and short QT syndromes, Brugada syndrome, early repolarization syndrome, acute myocardial ischemia, heart failure, hypertension, diabetes mellitus, obesity and highly trained athletes. Also the main pathophysiological mechanisms that explain the arrhythmogenic predisposition in these diseases and the basis for the VR markers are discussed. However, the same results have not been found in all conditions. Further studies are needed to reach a global consensus in order to incorporate these VR parameters in risk stratification of these patients.展开更多
AIM: To examine the effect of ibutilide on novel indexes of repolarization in patients with persistent atrial fibrillation (AF). METHODS: We studied consecutive patients scheduled for elective electrical cardioversion...AIM: To examine the effect of ibutilide on novel indexes of repolarization in patients with persistent atrial fibrillation (AF). METHODS: We studied consecutive patients scheduled for elective electrical cardioversion. Intravenous ibutilide (1+1mg) was administered before the electrical cardioversion while close electrocardiographic (ECG) monitoring was performed. ECG indexes such as corrected QT interval (QTc), the interval from the peak until the end of T wave (Tpe), and the Tpe/QT ratio were measured before ibutilide infusion and 10 min after the end of infusion. RESULTS: The final study population consisted of 20 patients (mean age: 67.1±9.9 years, 10 men). Six patients were cardioverted pharmacologically and did not proceed to electrical cardioversion. Two patientsdeveloped short non-sustained episodes of torsades de pointes ventricular tachycardia. All but one of the aforementioned ECG indexes increased significantly after ibutilide administration. In specific, the QTc interval increased from 442 ± 29 to 471 ± 37 ms (P=0.037), the Tpe interval in precordial leads from 96 ms (range 80-108 ms) to 101 ms (range 91-119 ms) (P=0.021), the Tpe interval in lead Ⅱ from 79 ms (range 70-88 ms) to 100 ms (range 87-104 ms) (P<0.001), the Tpe/QT ratio in precordial leads from 0.23 ms (range 0.18-0.26 ms) to 0.26 ms (range 0.23-0.28 ms) (P=0.028), and the Tpe interval dispersion from 25 ms (range 23-30 ms) to 35 ms (range 27-39 ms) (P=0.012). However, the Tpe/QT ratio in lead II did not change significantly. CONCLUSION: Ibutilide increases the duration and dispersion of ventricular repolarization. The prognostic value of Tpe and Tpe/QT in the setting of drug-induced proarrhythmia needs further study.展开更多
Ventricular repolarization is a complex electrical phenomenon which represents a crucial stage in electrical cardiac activity. It is expressed on the surface electrocardiogram by the interval between the start of the ...Ventricular repolarization is a complex electrical phenomenon which represents a crucial stage in electrical cardiac activity. It is expressed on the surface electrocardiogram by the interval between the start of the QRS complex and the end of the T wave or U wave(QT). Several physiological, pathological and iatrogenic factors can influence ventricular repolarization. It has been demonstrated that small perturbations in this process can be a potential trigger of malignant arrhythmias, therefore the analysis of ventricular repolarization represents an interesting tool to implement risk stratification of arrhythmic events in different clinical settings. The aim of this review is to critically revise the traditional methods of static analysis of ventricular repolarization as well as those for dynamic evaluation, their prognostic significance and the possible application in daily clinical practice.展开更多
BACKGROUND Diastolic electromechanical couple, a well-described phenomenon in symptomatic heart failure, has not been well studied in healthy people. We hypothesized that ventricular repolarization variables, such as ...BACKGROUND Diastolic electromechanical couple, a well-described phenomenon in symptomatic heart failure, has not been well studied in healthy people. We hypothesized that ventricular repolarization variables, such as the QT interval,Tpeak-to-Tend(Tpe) interval and Tpe/QT ratio, are associated with cardiac diastolic function in the healthy Chinese population.AIM To assess the relationship between ventricular repolarization variables and cardiac diastolic function in apparently healthy Chinese individuals.METHODS This was a community-based cross-sectional study conducted in Shenyang,China. A total of 414 healthy subjects aged 35-91 years were enrolled. All subjects underwent standard 12-lead electrocardiography(ECG) and comprehensive echocardiography. ECG enabled the measurement of QT and Tpe intervals and Tpe/QT ratio. echocardiographic parameters, such as the ratio of mitral early diastolic inflow velocity(E) and late diastolic inflow velocity(A), E-wave deceleration time, left atrial volume(LAV) and LAV index, were measured to assess diastolic function. E/A < 0.75 was considered to indicate reduced diastolic function. ECG and echocardiography results were analyzed separately and in a blinded fashion. Correlation and regression analyses were applied to determine associations.RESULTS Ventricular repolarization variables, such as the QTc interval(393.59 ± 26.74 vs403.86 ± 33.56; P < 0.001), Tpe interval(72.68 ± 12.41 vs 77.26 ± 17.86; P < 0.01),Tpec interval(76.36 ± 13.53 vs 83.32 ± 21.25; P < 0.001) and Tpe/QT ratio(0.19 ±0.03 vs 0.20 ± 0.04; P < 0.01), were significantly different between the normal diastolic function group and the reduced diastolic function group. Significant associations were found between repolarization variables and diastolic function.After adjusting for all other possible confounders, the QTc and Tpe_c intervals were significantly associated with the E/A ratio(P = 0.008; P = 0.010). In men, the QTc interval was associated with abnormal diastolic function, and compared to the third QTc tertile, in the second QTc tertile, the odds ratio was 0.257(95%CI:0.102–0.649; P = 0.004).CONCLUSION Repolarization variables are associated with cardiac diastolic function even in healthy people. Moderate levels of the QTc interval exert a protective effect on diastolic dysfunction in men.展开更多
BACKGROUND： The origin and classification of neural stem cells （NSCs） has been a subject of intense investigation for the past two decades. Efforts to categorize NSCs based on their location, function and expressio...BACKGROUND： The origin and classification of neural stem cells （NSCs） has been a subject of intense investigation for the past two decades. Efforts to categorize NSCs based on their location, function and expression have established that these cells are a heterogeneous pool in both the embryonic and adult brain. The discovery and additional characterization of adult NSCs has introduced the possibility of using these cells as a source for neuronal and glial replacement following injury or disease. To understand how one could manipulate NSC developmental programs for therapeutic use, additional work is needed to elucidate how NSCs are programmed and how signals during development are interpreted to determine cell fate. OBJECTIVE： This review describes the identification, classification and characterization of NSCs within the large neurogenic niche of the ventricular-subventricular zone （V-SVZ）. METHODS： A literature search was conducted using Pubmed including the keywords ＂ventricular-subventricular zone,＂ ＂neural stem cell,＂ ＂heterogeneity,＂ ＂identity＂ and/or ＂single cell＂ to find relevant manuscripts to include within the review. A special focus was placed on more recent findings using single-cell level analyses on neural stem cells within their niche（s）. RESULTS： This review discusses over 20 research articles detailing findings on V-SVZ NSC heterogeneity, over 25 articles describing fate determinants of NSCs, and focuses on 8 recent publications using distinct single-cell analyses of neural stem cells including fl0w cytometry and RNA-seq. Additionally, over 60 manuscripts highlighting the markers expressed on cells within the NSC lineage are included in a chart divided by cell type. CONCLUSIONS： Investigation of NSC heterogeneity and fate decisions is ongoing. Thus far, much research has been conducted in mice however, findings in human and other mammalian species are also discussed here. Implications of NSC heterogeneity established in the embryo for the properties of NSCs in the adult brain are explored, including how these cells may be redirected after injury or genetic manipulation.展开更多
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 model...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展开更多
Objective Background and Objects: Naturally occurring temporal variability of action potentialduration (APD) in isolated myocytes has been noted. Most of the studies have beenfocusing on analyzes of the differences in...Objective Background and Objects: Naturally occurring temporal variability of action potentialduration (APD) in isolated myocytes has been noted. Most of the studies have beenfocusing on analyzes of the differences in ionic channels and currents among theepicardial-, mid-myocardial-(M) and endocardial myocytes, and the rate-dependent (adaptation) characteristics of APD. We have found that the change in APD during achange in frequency of stimulation mostly reflects a change in rate of repolarization at distinct membrane potential levels. We assumed that in the myocytes, there is balancing mechanism, which is constantly adjusting the various ionic currents accommodating to the changing conditions. This intrinsic ability of adaptation is important and may offer some of the consequences of the transmural heterogeneity in adaptation of APD. This adaptive behaviors maybe equally important in maintaining the normal electrophysiological properties and in induction of arrhythmia in a case of error in normal adaptation. Though most studies of Na +/Ca 2+ exchange (NCX) has been emphasized on its reverse activaty during pathyological condition. Our hypothesis is that reverse activaty of NCX also plays an important role in adjusting the repolarization of AP during a physiological condition. A mismatch between action potential (AP) repolarization and relaxation of the contraction can be caused by intracellular Ca 2+ transport abnormalities. Ca 2+ influx via reverse activation of NCX can load the sarcoplasmic recticulum (SR), which has arrhythmogenic effect.Methods We studied the single myocytes from the left ventricle of adult mongrel dogs. During the cell separation, collagenase was perfused through LAD by Langandorff system. We use the patch-clamp system to determinded AP in current clamp mode. Myocyte contraction was imaged by a video camera, shortening of unloaded myocytes was detected by a video edge motion detector, using changes in light intensity at the edges of the myocyte. Results From 60 consecutive recorded APs at a constant 1.0 Hz stimulation under steady state conditions we found there is a variance in the repolarization between 10mV and-40mV. We also found the variance in the APD during the rate adaptation range of repolarization. Fluctuation in the transient may contribute to the APD variability. To test thishypothesis we block the transient by intracellular dialysis with 10 mM EGTA(n=19), this caused a significant reduction in the coefficient variability (CV=SD/mean APD%) from 2.3± 0.8 to 1.3± 0.3 P< 0.01. During a rate change of the stimulation from 0.6 Hz to 1.0 Hz. The AP duration increased from 278±8 msec to 320±9 msec, Mean+SD, n=5, 50 APs, P< 0.05. contraction is accompanied by an after-contraction(A-CON). The relaxation of contraction precedes the repolarization of the AP. We assumed that the enhancement of repolarization and the production of after-contraction can be possibly induced by reverse mode of NCX. Reducing [Na +] o by substitution of 40mM Na + with Li + favors NCX activating the reverse mode, which significantly decreased the dome of the AP from 4.8± 0.3 to -10.6± 1.2mV, P< 0.05, and increased the APD from 330±13 to 368±14 msec. P< 0.05.Conclusions Intracellular calcium transient most likely contributes to the beat-to-beat variance of action potential duration in canine ventricular myocyte. And it attributes to the voltage-dependent switch of NCX mode. Calcium concentration is high inmyocytes during the repolarization, and high intracellular Ca 2+ activates NCX in such a manner, that it generates an inward (positive, depolarizing) current. This current works against the repolarization, it is prolonging it, with other words it increases the duration of the action potential. The magnitude of calcium concentration during repolarization is very much dependent on calcium transport in the SR. The calcium transport in the SR is subject to adrenergic actions, and other physiologic and pathologic regulators. Under pathologic conditions展开更多
Objective To examine the relationship between Tpeak- Tend interval （Tpe） and Tpe/QT ratio with occurrence of ventricular premature beats （VPBs） and left ventricular remodeling in hypertension. Methods A total of 5...Objective To examine the relationship between Tpeak- Tend interval （Tpe） and Tpe/QT ratio with occurrence of ventricular premature beats （VPBs） and left ventricular remodeling in hypertension. Methods A total of 52 patients with mild to moderate essential hypertension were included, undergoing echocardiography and 24-hours Holter monitoring. Ventricular remodeling was assessed by left ventricular mass index （LVMI） using the Devereux formula and diastolic fimction by transmitral E and A wave velocities and E/A ratio. Tpe was measured in the precordial leads. The end of the T wave was set by the method of the tangent to the steepest descending slope of the T wave. Results Tpe and Tpe/QT in leads V2 （r = 0.33, P = 0.01; r = 0.27, P = 0.04 respectively） and V3 （r = 0.40, P = 0.002; r = 0.40, P = 0.003, respectively） correlated significantly with LVMI. A significant inverse relationship was observed between E/A ratio and QT （r = -0.33, P = 0.01）, Tpe in V3 （r = -0.39, P = 0.003） and Tpe/QT in V3 （r = -0.31, P = 0.02）. Tpe in V3, V5, mean Tpe and maximum Tpe with cut-offvalues of 60 ms, 59 ms, 62 ms and 71 ms, respectively, associated with the occurrence of ventricular premature beats. Conclusions The repolarization parameters Tpe interval and Tpe/QT ratio correlate with LVMI and indices of left ventricular diastolic function and show better predictive values than traditional parameters such as QT interval and QT dispersion. Lead V3 is the best lead for measuring Tpe and Tpe/QT. These ECG indices can therefore be used in clinical practice to monitor LV remodeling and predict occurrence of VPBs.展开更多
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...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.展开更多
The 12-lead electrocardiogram(ECG) is still the most used tool in cardiology clinical practice. Considering its easy accessibility, low cost and the information that it provides, it remains the starting point for diag...The 12-lead electrocardiogram(ECG) is still the most used tool in cardiology clinical practice. Considering its easy accessibility, low cost and the information that it provides, it remains the starting point for diagnosis and prognosis. More specifically, its ability to detect prognostic markers for sudden cardiac death due to arrhythmias by identifying specific patterns that express electrical disturbances of the heart muscle, which may predispose to malignant arrhythmias, is universally recognized. Alterations in the ventricular repolarization process, identifiable on a 12-lead ECG, play a role in the genesis of ventricular arrhythmias in different cardiac diseases. The aim of this paper is to focus the attention on a new marker of arrhythmic risk, the early repolarization pattern in order to highlight the prognostic role of the 12-lead ECG.展开更多
文摘Summary： To study the effect of of lidocaine and amiodarone on the transmural heterogeneity of ventricular repolarization in isolated rabbit hearts model of sustained global ischemia and to explore the mechanisms underlying the antiarrhythmic activity of lidocaine and amiodarone, rabbits were randomly divided into 4 groups： control group, ischemia group, lidocaine group and amiodarone group. By the monophasic action potential （MAP） recording technique, MAPs of epicardium, midmyocardium and endocardium were simultaneously recorded across the left ventricular free wall in rabbit hearts perfused by low-flow ischemia （2. 5 mL/min） in Langendorff method to study the transmural dispcrsion of repolarization （TDR） and arrhythmic induced by ischemia.Our results showed that TDR of three myocardial layers in ischemia group were significantly lengthened after ischemia. TDR was increased from 17.5±3.9 ms to 31.2±4.6 ms at the time that concided with the onset of sustained ventricle arrhythmic. Amiodarone could decrease TDR, but lidocaine could increase TDR at initial ischemia, and no significant difference was found at other ischemia time points. 5 cases had ventriclar arrhythmia in ischemia group （62. 5%）, but no case in lidocaine group （P〈0.01） and only 1 case in amiodarone group had ventrilar arrhythmia （P〈 0.01）. No significant difference was found between amiodarone group and lidocaine group. It is concluded that TDR of of three myocardial layers increases significantly at ischemia and it is closely associated with development of ventricular arrhythmia, and amiodarone could decrease TDR, but lidocaine could increase TDR at initial ischemia and has no effects at other ischemia time points.
文摘Objective:To observe effects of hypokalemia on transmural heterogeneity of ventricular repolarization in left ventricular myocardium of rabbit,and explore the role of hypokalemia in malignant ventricular arrhythmia（MVA）.Methods:A total of 20 rabbits were randomly divided into control group and hypokalemic group.Isolated hearts in the control group were simply perfused with modified Tyrode’s solution,and were perfused with hypokalemic Tyrode’s solution in hypokalemic group.Ventricular fibrillation threshold（VFT）,90%monophasic action potential repolarization duration(APD<sub>90</sub>) of subepicardial,midmyocardial and subendocardial myocardium,transmural dispersion of repolarization（TDR） and Cx43 protein expression in three layers of myocardium were measured in both groups.Results:VFT in the control group and the hypokalemic group were（13.40±2.95） V,and（7.00±1.49） V,respectively.There was a significant difference between two groups（P【0.01）.APD<sub>90</sub> of three myocardial layers in the hypokalemic group were significantly prolonged than those in the control group（/’【0.01）.△APD<sub>90</sub>in the hypokalemic group and the control group were（38.10±10\29） ms and（23.7015.68） ms,and TDR were（52.90<sub>r</sub> 14.55） ms and（36.10±12.44） ms,respectively.△APD<sub>90</sub> and TDR in the hypokalemic group were significantly higher than those in the control group(P【0.05|,and the increase in△APD<sub>90</sub> of midmyocardium was more significant in the hypokalemic group.Cx43 protein expression of all three myocardial layers were decreased significantly in the hypokalemic group（P【0.01）, and△APD<sub>90</sub> was significantly increased {P【0.05).Reduction of Cx43 protein expression was more significant in the midmyocardium.Conclusions:Hypokalemic can increase transmural heterogeneity of Cx43 expression and repolarization in left ventricular myocardium of rabbit,and decrease VFT and can induce MVA more easily.
文摘Objective: Although after pacing animal and human studies have demonstrated a rate-dependent effect of sotalol on ventricular repolarization, there is little information on the effects of sotalol on ventricular repolarization during exercise. This study attempted to show the effects of sotalol on ventricular repolarization during physiological exercise. Methods: Thirty-one healthy volunteers (18 males, 13 females) were enrolled in the study. Each performed a maximal treadmill exercise test according to the Bruce protocol after random treatment with sotalol, propranolol and placebo. Results: Sotalol significantly prolonged QTc (corrected QT) and JTc (corrected JT) intervals at rest compared with propranolol (QTc 324.86 ms vs 305.21 ms, P<0.001; JTc 245.04 ms vs 224.17 ms, P<0.001) and placebo (QTc 324.86 ms vs 314.06 ms, P<0.01; JTc 245.04 ms vs. 232.69 ms, P<0.001). The JTc percent reduction increased progressively with each stage of exercise and correlated positively with exercise heart rate (r=0.148, P<0.01). The JTc percent reduction correlation with exercise heart rate did not exist with either propranolol or placebo. Conclusions: These results imply that with sotalol ventricular repolarization is progressively shortened after exercise. Thus the specific class III antiarrhythmic activity of sotalol, present as delay of ventricular repolarization, may be attenuated during exercise. Such findings may imply the need to consider other antiarrythmic therapy during periods of stress-induced tachycardia.
文摘This study aimed to describe the epidemiology of repolarization dispersion (QT dispersion and Tpeak-Tend dispersion) and further describe their associated clinical correlates among uncontrolled arterial hypertension in type-2 Diabetics patient, in western region of the Republic of Macedonia. Abnormal ventricular repolarization is associated with increased cardiovascular risk. Data relating to the frequency of increased repolarization dispersion, among uncontrolled arterial hypertension in type-2 Diabetics patient in western region of the Republic of Macedonia, are scarce. A total of 600 patients were enrolled into this observation study. Study participans were selected among primary care patient, who were receiving ongoing care for diabetes mellitus and hypertension during 1 calendar year. Twelve lead resting electrocardiography, QT, QTc, Tpeak-Tend-intervals and dispersions, were determined manually, and were compared between groups. Patients with uncontrolled BP have greater frequency of: prolonged QTc.max.interval, (61.3% vs.33.6%;p = 0.0005), prolonged Tpeak-Tend interval (65.3% vs. 34.7%;p = 0.005), increased dispersion of QTc. interval (65.9% vs. 34.1%;p = 0.00), increased disperion of Tpeak-Tend interval (65.5% vs. 34.5%;p = 0.002). Females with uncontrolled BP have greater frequency of: increased dispersion of QTc. interval (61.2% vs. 38%;p = 0.02), increased dispersion of Tpeak-Tend interval (63.1% vs. 31.5%;p = 0.008). Hypertensive diabetic patients with uncontrolled BP and abnormal ventricular repolarization have greater BMI (p = 0.000;95%CI 3.849 - 7.871), longer duration of D.M (p = 0.000;95%CI 1.600 - 1.981), longer duration of arterial hypertension (p = 0.000;95%CI 1.468 - 1.850) and less controlled glycemia (p = 0.000;95%CI 1.556 - 3.004). Frequency of increased set of electrophysiological parameters that indicate a prolonged and more heterogeneous repolarization among diabetic patients with uncontrolled BP, is considerable high and seems to be significantly associated with demographic and clinical parameters: gender, BMI, duration of diabetes, duration of BP and glycemic control.
文摘Malignant cardiac arrhythmias which result in sudden cardiac death may be present in individuals apparently healthy or be associated with other medical conditions. The way to predict their appearance represents a challenge for the medical community due to the tragic outcomes in most cases. In the last two decades some ventricular repolarization(VR) markers have been found to be useful to predict malignant cardiac arrhythmias in several clinical conditions. The corrected QT, QT dispersion, Tpeak-Tend, Tpeak-Tend dispersion and Tp-e/QT have been studied and implemented in clinical practice for this purpose. These markers are obtained from 12 lead surface electrocardiogram. In this review we discuss how these markers have demonstrated to be effective to predict malignant arrhythmias in medical conditions such as long and short QT syndromes, Brugada syndrome, early repolarization syndrome, acute myocardial ischemia, heart failure, hypertension, diabetes mellitus, obesity and highly trained athletes. Also the main pathophysiological mechanisms that explain the arrhythmogenic predisposition in these diseases and the basis for the VR markers are discussed. However, the same results have not been found in all conditions. Further studies are needed to reach a global consensus in order to incorporate these VR parameters in risk stratification of these patients.
文摘AIM: To examine the effect of ibutilide on novel indexes of repolarization in patients with persistent atrial fibrillation (AF). METHODS: We studied consecutive patients scheduled for elective electrical cardioversion. Intravenous ibutilide (1+1mg) was administered before the electrical cardioversion while close electrocardiographic (ECG) monitoring was performed. ECG indexes such as corrected QT interval (QTc), the interval from the peak until the end of T wave (Tpe), and the Tpe/QT ratio were measured before ibutilide infusion and 10 min after the end of infusion. RESULTS: The final study population consisted of 20 patients (mean age: 67.1±9.9 years, 10 men). Six patients were cardioverted pharmacologically and did not proceed to electrical cardioversion. Two patientsdeveloped short non-sustained episodes of torsades de pointes ventricular tachycardia. All but one of the aforementioned ECG indexes increased significantly after ibutilide administration. In specific, the QTc interval increased from 442 ± 29 to 471 ± 37 ms (P=0.037), the Tpe interval in precordial leads from 96 ms (range 80-108 ms) to 101 ms (range 91-119 ms) (P=0.021), the Tpe interval in lead Ⅱ from 79 ms (range 70-88 ms) to 100 ms (range 87-104 ms) (P<0.001), the Tpe/QT ratio in precordial leads from 0.23 ms (range 0.18-0.26 ms) to 0.26 ms (range 0.23-0.28 ms) (P=0.028), and the Tpe interval dispersion from 25 ms (range 23-30 ms) to 35 ms (range 27-39 ms) (P=0.012). However, the Tpe/QT ratio in lead II did not change significantly. CONCLUSION: Ibutilide increases the duration and dispersion of ventricular repolarization. The prognostic value of Tpe and Tpe/QT in the setting of drug-induced proarrhythmia needs further study.
文摘Ventricular repolarization is a complex electrical phenomenon which represents a crucial stage in electrical cardiac activity. It is expressed on the surface electrocardiogram by the interval between the start of the QRS complex and the end of the T wave or U wave(QT). Several physiological, pathological and iatrogenic factors can influence ventricular repolarization. It has been demonstrated that small perturbations in this process can be a potential trigger of malignant arrhythmias, therefore the analysis of ventricular repolarization represents an interesting tool to implement risk stratification of arrhythmic events in different clinical settings. The aim of this review is to critically revise the traditional methods of static analysis of ventricular repolarization as well as those for dynamic evaluation, their prognostic significance and the possible application in daily clinical practice.
基金Supported by the National Basic Research Program of China,No.973-Program#2007CB507405
文摘BACKGROUND Diastolic electromechanical couple, a well-described phenomenon in symptomatic heart failure, has not been well studied in healthy people. We hypothesized that ventricular repolarization variables, such as the QT interval,Tpeak-to-Tend(Tpe) interval and Tpe/QT ratio, are associated with cardiac diastolic function in the healthy Chinese population.AIM To assess the relationship between ventricular repolarization variables and cardiac diastolic function in apparently healthy Chinese individuals.METHODS This was a community-based cross-sectional study conducted in Shenyang,China. A total of 414 healthy subjects aged 35-91 years were enrolled. All subjects underwent standard 12-lead electrocardiography(ECG) and comprehensive echocardiography. ECG enabled the measurement of QT and Tpe intervals and Tpe/QT ratio. echocardiographic parameters, such as the ratio of mitral early diastolic inflow velocity(E) and late diastolic inflow velocity(A), E-wave deceleration time, left atrial volume(LAV) and LAV index, were measured to assess diastolic function. E/A < 0.75 was considered to indicate reduced diastolic function. ECG and echocardiography results were analyzed separately and in a blinded fashion. Correlation and regression analyses were applied to determine associations.RESULTS Ventricular repolarization variables, such as the QTc interval(393.59 ± 26.74 vs403.86 ± 33.56; P < 0.001), Tpe interval(72.68 ± 12.41 vs 77.26 ± 17.86; P < 0.01),Tpec interval(76.36 ± 13.53 vs 83.32 ± 21.25; P < 0.001) and Tpe/QT ratio(0.19 ±0.03 vs 0.20 ± 0.04; P < 0.01), were significantly different between the normal diastolic function group and the reduced diastolic function group. Significant associations were found between repolarization variables and diastolic function.After adjusting for all other possible confounders, the QTc and Tpe_c intervals were significantly associated with the E/A ratio(P = 0.008; P = 0.010). In men, the QTc interval was associated with abnormal diastolic function, and compared to the third QTc tertile, in the second QTc tertile, the odds ratio was 0.257(95%CI:0.102–0.649; P = 0.004).CONCLUSION Repolarization variables are associated with cardiac diastolic function even in healthy people. Moderate levels of the QTc interval exert a protective effect on diastolic dysfunction in men.
文摘BACKGROUND： The origin and classification of neural stem cells （NSCs） has been a subject of intense investigation for the past two decades. Efforts to categorize NSCs based on their location, function and expression have established that these cells are a heterogeneous pool in both the embryonic and adult brain. The discovery and additional characterization of adult NSCs has introduced the possibility of using these cells as a source for neuronal and glial replacement following injury or disease. To understand how one could manipulate NSC developmental programs for therapeutic use, additional work is needed to elucidate how NSCs are programmed and how signals during development are interpreted to determine cell fate. OBJECTIVE： This review describes the identification, classification and characterization of NSCs within the large neurogenic niche of the ventricular-subventricular zone （V-SVZ）. METHODS： A literature search was conducted using Pubmed including the keywords ＂ventricular-subventricular zone,＂ ＂neural stem cell,＂ ＂heterogeneity,＂ ＂identity＂ and/or ＂single cell＂ to find relevant manuscripts to include within the review. A special focus was placed on more recent findings using single-cell level analyses on neural stem cells within their niche（s）. RESULTS： This review discusses over 20 research articles detailing findings on V-SVZ NSC heterogeneity, over 25 articles describing fate determinants of NSCs, and focuses on 8 recent publications using distinct single-cell analyses of neural stem cells including fl0w cytometry and RNA-seq. Additionally, over 60 manuscripts highlighting the markers expressed on cells within the NSC lineage are included in a chart divided by cell type. CONCLUSIONS： Investigation of NSC heterogeneity and fate decisions is ongoing. Thus far, much research has been conducted in mice however, findings in human and other mammalian species are also discussed here. Implications of NSC heterogeneity established in the embryo for the properties of NSCs in the adult brain are explored, including how these cells may be redirected after injury or genetic manipulation.
文摘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
文摘Objective Background and Objects: Naturally occurring temporal variability of action potentialduration (APD) in isolated myocytes has been noted. Most of the studies have beenfocusing on analyzes of the differences in ionic channels and currents among theepicardial-, mid-myocardial-(M) and endocardial myocytes, and the rate-dependent (adaptation) characteristics of APD. We have found that the change in APD during achange in frequency of stimulation mostly reflects a change in rate of repolarization at distinct membrane potential levels. We assumed that in the myocytes, there is balancing mechanism, which is constantly adjusting the various ionic currents accommodating to the changing conditions. This intrinsic ability of adaptation is important and may offer some of the consequences of the transmural heterogeneity in adaptation of APD. This adaptive behaviors maybe equally important in maintaining the normal electrophysiological properties and in induction of arrhythmia in a case of error in normal adaptation. Though most studies of Na +/Ca 2+ exchange (NCX) has been emphasized on its reverse activaty during pathyological condition. Our hypothesis is that reverse activaty of NCX also plays an important role in adjusting the repolarization of AP during a physiological condition. A mismatch between action potential (AP) repolarization and relaxation of the contraction can be caused by intracellular Ca 2+ transport abnormalities. Ca 2+ influx via reverse activation of NCX can load the sarcoplasmic recticulum (SR), which has arrhythmogenic effect.Methods We studied the single myocytes from the left ventricle of adult mongrel dogs. During the cell separation, collagenase was perfused through LAD by Langandorff system. We use the patch-clamp system to determinded AP in current clamp mode. Myocyte contraction was imaged by a video camera, shortening of unloaded myocytes was detected by a video edge motion detector, using changes in light intensity at the edges of the myocyte. Results From 60 consecutive recorded APs at a constant 1.0 Hz stimulation under steady state conditions we found there is a variance in the repolarization between 10mV and-40mV. We also found the variance in the APD during the rate adaptation range of repolarization. Fluctuation in the transient may contribute to the APD variability. To test thishypothesis we block the transient by intracellular dialysis with 10 mM EGTA(n=19), this caused a significant reduction in the coefficient variability (CV=SD/mean APD%) from 2.3± 0.8 to 1.3± 0.3 P< 0.01. During a rate change of the stimulation from 0.6 Hz to 1.0 Hz. The AP duration increased from 278±8 msec to 320±9 msec, Mean+SD, n=5, 50 APs, P< 0.05. contraction is accompanied by an after-contraction(A-CON). The relaxation of contraction precedes the repolarization of the AP. We assumed that the enhancement of repolarization and the production of after-contraction can be possibly induced by reverse mode of NCX. Reducing [Na +] o by substitution of 40mM Na + with Li + favors NCX activating the reverse mode, which significantly decreased the dome of the AP from 4.8± 0.3 to -10.6± 1.2mV, P< 0.05, and increased the APD from 330±13 to 368±14 msec. P< 0.05.Conclusions Intracellular calcium transient most likely contributes to the beat-to-beat variance of action potential duration in canine ventricular myocyte. And it attributes to the voltage-dependent switch of NCX mode. Calcium concentration is high inmyocytes during the repolarization, and high intracellular Ca 2+ activates NCX in such a manner, that it generates an inward (positive, depolarizing) current. This current works against the repolarization, it is prolonging it, with other words it increases the duration of the action potential. The magnitude of calcium concentration during repolarization is very much dependent on calcium transport in the SR. The calcium transport in the SR is subject to adrenergic actions, and other physiologic and pathologic regulators. Under pathologic conditions
文摘Objective To examine the relationship between Tpeak- Tend interval （Tpe） and Tpe/QT ratio with occurrence of ventricular premature beats （VPBs） and left ventricular remodeling in hypertension. Methods A total of 52 patients with mild to moderate essential hypertension were included, undergoing echocardiography and 24-hours Holter monitoring. Ventricular remodeling was assessed by left ventricular mass index （LVMI） using the Devereux formula and diastolic fimction by transmitral E and A wave velocities and E/A ratio. Tpe was measured in the precordial leads. The end of the T wave was set by the method of the tangent to the steepest descending slope of the T wave. Results Tpe and Tpe/QT in leads V2 （r = 0.33, P = 0.01; r = 0.27, P = 0.04 respectively） and V3 （r = 0.40, P = 0.002; r = 0.40, P = 0.003, respectively） correlated significantly with LVMI. A significant inverse relationship was observed between E/A ratio and QT （r = -0.33, P = 0.01）, Tpe in V3 （r = -0.39, P = 0.003） and Tpe/QT in V3 （r = -0.31, P = 0.02）. Tpe in V3, V5, mean Tpe and maximum Tpe with cut-offvalues of 60 ms, 59 ms, 62 ms and 71 ms, respectively, associated with the occurrence of ventricular premature beats. Conclusions The repolarization parameters Tpe interval and Tpe/QT ratio correlate with LVMI and indices of left ventricular diastolic function and show better predictive values than traditional parameters such as QT interval and QT dispersion. Lead V3 is the best lead for measuring Tpe and Tpe/QT. These ECG indices can therefore be used in clinical practice to monitor LV remodeling and predict occurrence of VPBs.
基金supported by a grant from the Natural Science Foundation of Hubei(2007ABA288)
文摘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.
文摘The 12-lead electrocardiogram(ECG) is still the most used tool in cardiology clinical practice. Considering its easy accessibility, low cost and the information that it provides, it remains the starting point for diagnosis and prognosis. More specifically, its ability to detect prognostic markers for sudden cardiac death due to arrhythmias by identifying specific patterns that express electrical disturbances of the heart muscle, which may predispose to malignant arrhythmias, is universally recognized. Alterations in the ventricular repolarization process, identifiable on a 12-lead ECG, play a role in the genesis of ventricular arrhythmias in different cardiac diseases. The aim of this paper is to focus the attention on a new marker of arrhythmic risk, the early repolarization pattern in order to highlight the prognostic role of the 12-lead ECG.
