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Ventricular Repolarization (ventricular + repolarization)
Selected AbstractsThe Effect of Antihistamine Cetirizine on Ventricular Repolarization in Congenital Long QT SyndromeJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 7 2007ANNA-MARI HEKKALA M.D. Introduction: Many drugs are known to block cardiac potassium channels, thus prolonging QT interval and predisposing to malignant arrhythmias. Patients with congenital long QT syndrome are particularly vulnerable, but usually electrophysiological effects of drugs have not been assessed in these patients at risk. Methods: Fifteen asymptomatic patients with type 1 (LQT1), 15 patients with type 2 (LQT2) long QT syndrome, and 15 healthy volunteers took a placebo and cetirizine 10 mg. In addition, healthy volunteers took cetirizine 50 mg. The study was single-blinded and randomized. Exercise tests were performed during stable plasma concentrations. The electrocardiogram was recorded with a body surface potential mapping system (BSPM). Data were analyzed with an automated analyze program. QT intervals to the T wave apex and T wave end and their difference (Tp-e) were determined at rest and at specified heart rates during and after exercise. Results: Cetirizine did not lengthen the QT intervals at rest or during exercise and recovery in any group. It shortened Tp-e at rest in LQT1 and LQT2 patients and during exercise test in LQT1 patients, thus slightly decreasing electrocardiographic transmural dispersion of repolarization. Conclusions: Cetirizine does not adversely modify ventricular repolarization in types 1 and 2 long QT syndrome, suggesting that it might be used safely in these long QT syndrome patients. [source] QT Dispersion Does Not Represent Electrocardiographic Interlead Heterogeneity of Ventricular RepolarizationJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 8 2000MAREK MALIK Ph.D. QT Dispersion and Repolarization Heterogeneity. Introduction: QT dispersion (QTd, range of QT intervals in 12 ECG leads) is thought to reflect spatial heterogeneity of ventricular refractoriness. However, QTd may be largely due to projections of the repolarization dipole rather than "nondipolar" signals. Methods and Results: Seventy-eight normal subjects (47 ± 16 years, 23 women), 68 hypertrophic cardiomyopathy patients (HCM; 38 ± 15 years. 21 women), 72 dilated cardiomyopathy patients (DCM; 48 ± 15 years, 29 women), and 81 survivors of acute myocardial infarction (AMI; 63 ± 12 years, 20 women) had digital 12-lead resting supine ECGs recorded (10 ECGs recorded in each subject and results averaged). In each ECG lead, QT interval was measured under operator review by QT Guard (GE Marquette) to obtain QTd. QTd was expressed as the range, standard deviation, and highest-to-lowest quartile difference of QT interval in all measurable leads. Singular value decomposition transferred ECGs into a minimum dimensional time orthogonal space. The first three components represented the ECG dipole; other components represented nondipolar signals. The power of the T wave nondipolar within the total components was computed to measure spatial repolarization heterogeneity (relative T wave residuum, TWR). OTd was 33.6 ± 18.3, 47.0 ± 19.3, 34.8 ± 21.2, and 57.5 ± 25.3 msec in normals, HCM, CM, and AMI, respectively (normals vs DCM: NS, other P < 0.009). TWR was 0.029%± 0.031%, 0.067%± 0.067%, 0.112%± 0.154%, and 0.186%± 0.308% in normals, HCM, DCM, and AMI (HCM vs DCM: NS. other P < 0.006), The correlations between QTd and TWR were r = -0.0446, 0.2805, -0.1531, and 0.0771 (P = 0.03 for HCM, other NS) in normals, HCM, DCM, and AMI, respectively. Conclusion: Spatial heterogeneity of ventricular repolarization exists and is measurable in 12-lead resting ECGs. It differs between different clinical groups, but the so-called QT dispersion is unrelated to it. [source] Changes in Left Ventricular Repolarization and Ion Channel Currents Following a Transient Rate Increase Superimposed on Bradycardia in Anesthetized DogsJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 6 2000MICHAEL RUBART M.D. Electrical Remodeling of the Heart due to Rate. Introduction: We previously demonstrated in dogs that a transient rate increase superimposed on bradycardia causes prolongation of ventricular refractoriness that persists for hours after resumption of bradycardia. In this study, we examined changes in membrane currents that are associated with this phenomenon. Methods and Results: The whole cell, patch clamp technique was used to record transmembrane voltages and currents, respectively, in single mid-myocardial left ventricular myocytes from dogs with 1 week of complete AV block; dogs either underwent 1 hour of left ventricular pacing at 120 beats/min or did not undergo pacing. Pacing significantly heightened mean phase 1 and peak plateau amplitudes by ,6 and ,3 mV, respectively (P < 0.02). and prolonged action potential duration at 90% repolarization from 235 ± 8 msec to 278 ± 8 msec (1 Hz; P = 0.02). Rapid pacing-induced changes in transmembrane ionic currents included (1) a more pronounced cumulative inactivation of the 4-aminopyridine-sensitive transient outward K+ current, I to over the range of physiologic frequencies, resulting from a ,30% decrease in the population of quickly reactivating channels; (2) increases in peak density of L-type Ca2+ currents, Ica.I.' by 15% to 35% between +10 and +60 mV; and (3) increases in peak density of the Ca2+ -activated chloride current, ICl.Ca' by 30% to 120% between +30 and +50 mV. Conclusion: Frequency-dependent reduction in Ito combined with enhanced ICa.I. causes an increase in net inward current that may he responsible for the observed changes in ventricular repolarization. This augmentation of net cation influx is partially antagonized by an increase in outward ICa.Cl. [source] T-Wave Variability Detects Abnormalities in Ventricular Repolarization: A Prospective Study Comparing Healthy Persons and Olympic AthletesANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 3 2009Lara Heinz M.D. Background: Sudden cardiac death in athletes is more common than in the general population. Routine screening procedures are performed to identify competitors at risk. A new Holter-based parameter analyzes variation of the ventricular repolarization (TVar). The aim of this study was to evaluate differences in electrocardiogram (ECG), Echo, and Holter (H) in competitive athletes compared to a healthy control group consisting of medical students (MS). Methods: A total of 40 athletes (19 females, Olympic team, Luxembourg) and 40 MS (22 females) were examined by means of a resting ECG, treadmill exercise (TE), echocardiogram (Echo), as well as H recordings during a routine screening visit. To analyze TVar, a 20-minute H recording at rest (sampling rate 1000 per second) was performed. Moreover, heart rate variability (HRV) as well as HR turbulence (HRT) was computed. Results: No differences in demographic variables were detected. Quantification of HRV detected a significant increase in the vagal component of autonomic cardiac modulation. In contrast, no differences for HRT were found. Echo parameter demonstrated a thicker septal wall without differences of the posterior wall. TVar values were normal in range, but did differ significantly between the two groups. No correlation between TVar and echo as well as Holter parameters was detected. Conclusions: TVar was able to demonstrate significant differences in terms of alterations of ventricular activation. This might indicate an early change of myocardial repolarization representing a substrate for life-threatening arrhythmia. Larger studies on the predictive value of TVar including follow-up are necessary to confirm this preliminary finding. [source] Dynamics of Ventricular Repolarization in Patients with Dilated Cardiomyopathy Versus Healthy SubjectsANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 2 2005Jose Luis Alonso M.D. Background: Patients with impaired left ventricular function have a high risk of developing ventricular arrhythmias and sudden death. Among different markers of risk, the prolongation and regional heterogeneity of repolarization are of increasing interest. However, there are limited data regarding feasibility of analyzing repolarization parameters and their dynamics in 24-hour Holter ECG recordings. Methods: Dynamic behavior of repolarization parameters was studied with a new automatic algorithm in digital 24-hour Holter recordings of 60 healthy subjects and 55 patients with idiopathic dilated cardiomyopathy (IDC). Repolarization parameters included the mean value of QT and QTc durations, QT dispersion, and peaks of QT duration and QT dispersion above prespecified thresholds. Results: In comparison to healthy subjects, patients with IDC had lower heart rate variability, longer mean QT and QTc durations, higher content of QTc peaks >500 ms, longer QT dispersion and its standard deviation, and a higher content of peaks >100 ms of QT dispersion (P < 0.01 for all comparisons). These repolarization parameters were significantly higher in IDC patients after adjustment for age, sex, and heart rate variability. The parameters of repolarization dynamics correlated with SDNN in healthy subjects but not in dilated cardiomyopathy patients. Conclusions: The automatic assessment of repolarization parameters in 24-hour digital ECG recordings is feasible and differentiates dilated cardiomyopathy patients from healthy subjects. Patients with dilated cardiomyopathy have increased QT duration, QT dispersion, and increased variability of QT dispersion reflecting variations in T-wave morphology, the factors which might predispose them to the development of arrhythmic events. [source] Differences between Ventricular Repolarization in Men and Women: Description, Mechanism and ImplicationsANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 4 2003Borys Surawicz M.D., M.A.C.C. The purpose of this review article is to discuss the differences between ventricular repolarization in males and females in terms of morphology, possible mechanism, and practical significance. The interest in the subject increased when it became known that in comparison to men, women have a higher incidence of torsade de pointes (tdp) and a greater lengthening of QT-interval after administration of class III antiarrhythmic drugs. Before puberty, the QT intervals and the patterns of ventricular repolarization in boys and girls are similar. At puberty, in boys the QT interval shortens, and a typical male pattern of ventricular repolarization develops. This pattern is characterized by a higher amplitude of the J-point, a shorter and steeper ST segment course, a steeper ascent, and a higher amplitude of the T wave. This pattern is prevalent in >90% of young males. With increasing age the prevalence of the male pattern in males declines gradually and drops to 14% in the oldest age group. The rise and fall of the prevalence of the male pattern appears to parallel the rise and decline of testosterone in males. The female pattern of ventricular repolarization is prevalent in about 80% of females in all age groups. The hormonal effects on ventricular repolarization have been studied in normal and castrated rabbits of both sexes. The available evidence indicates that the females have greater divergence of L calcium current among different layers of the myocardium and a lower density of the repolarizing Kr and Ks currents. The clinical significance of the repolarization differences among genders remains to be determined. Of particular interest is the question whether the males with female pattern are at the same risk of tdp as the females or whether the females with male pattern are at lower risk of tdp than the females with female pattern. [source] Electrocardiographic Quantitation of Heterogeneity of Ventricular RepolarizationANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 1 2000Peter M. Okin M.D. Background:QT interval dispersion (QTd) measured from the surface ECG has emerged as the most common noninvasive method for assessing heterogeneity of ventricular repolarization. Although QTd correlates with dispersion of monophasic action potential duration at 90% repolarization and with dispersion of recovery time recorded from the epicardium, total T-wave area, representing a summation of vectors during this time interval, has been shown to have the highest correlation with these invasive measures of dispersion of repolarization. However, recent clinical studies suggest that the ratio of the second to first eigenvalues of the spatial T-wave vector using principal component analysis (PCA ratio) may more accurately reflect heterogeneity of ventricular repolarization. Methods:To better characterize the ECG correlates of surface ECG measures of heterogeneity of ventricular repolarization and to establish normal values of these criteria using an automated measurement method, the relations of QRS onset to T-wave offset (QTod) and to T-wave peak (QTpd) dispersion and the PCA ratio to T-wave area and amplitude, heart rate, QRS axis and duration, and the QTo interval were examined in 163 asymptomatic subjects with normal resting ECGs and normal left ventricular mass and function. QTod and QTpd were measured by computer from digitized ECGs as the difference between the maximum and minimum QTo and QTp intervals, respectively. Results:In univariate analyses, a significant correlation was found between the sum of the T-wave area and the PCA ratio (R =,0.46, P < 0.001), but there was no significant correlation of the sum of T-wave area with QTod (R = 0.11, P = NS) or QTpd (R=0.09, P = NS). There were only modest correlations between QTod and QTpd (R = 0.45) and between the PCA ratio and QTod (R = 0.29) and QTpd (R = 0.49) (each P < 0.001). In stepwise multivariate linear regression analyses, the PCA ratio was significantly related to the sum of T-wave area, T-wave amplitude in aVL, and to female gender (overall R = 0.54, P < 0.001), QTod correlated only with the maximum QTo0 interval (R = 0.39, P < 0.001), and QTpd was related to heart rate and QRS axis (overall R = 0.36, P <0.001). In addition, the normal interlead dispersion of repolarization as measured by QTod was significantly greater than dispersion measured by QTod (23.5 ± 11.5 ms vs 18.3 ± 11.2 ms, P < 0.001). Conclusions: These findings provide new information on ECG measures of heterogeneity of repolarization in normal subjects, with a significantly higher intrinsic variability of Q to T-peak than Q to T-offset dispersion and only modest correlation between these wo measures. The independent relation of the PCA ratio to the sum of T-wave area suggests that the PCA ratio may be a more accurate surface ECG reflection of the heterogeneity of ventricular repolarizat on. A.N.E. 2000;5(1):79,87 [source] The Time Course of New T-Wave ECG Descriptors Following Single- and Double-Dose Administration of Sotalol in Healthy SubjectsANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 1 2010Fabrice Extramiana M.D., Ph.D. Introduction: The aim of the study was to assess the time course effect of IKr blockade on ECG biomarkers of ventricular repolarization and to evaluate the accuracy of a fully automatic approach for QT duration evaluation. Methods: Twelve-lead digital ECG Holter was recorded in 38 healthy subjects (27 males, mean age = 27.4 ± 8.0 years) on baseline conditions (day 0) and after administration of 160 mg (day 1) and 320 mg (day 2) of d-l sotalol. For each 24-hour period and each subject, ECGs were extracted every 10 minutes during the 4-hour period following drug dosage. Ventricular repolarization was characterized using three biomarker categories: conventional ECG time intervals, principal component analysis (PCA) analysis on the T wave, and fully automatic biomarkers computed from a mathematical model of the T wave. Results: QT interval was significantly prolonged starting 1 hour 20 minutes after drug dosing with 160 mg and 1 hour 10 minutes after drug dosing with 320 mg. PCA ventricular repolarization parameters sotalol-induced changes were delayed (>3 hours). After sotalol dosing, the early phase of the T wave changed earlier than the late phase prolongation. Globally, the modeled surrogate QT paralleled manual QT changes. The duration of manual QT and automatic surrogate QT were strongly correlated (R2= 0.92, P < 0.001). The Bland and Altman plot revealed a nonstationary systematic bias (bias = 26.5 ms ± 1.96*SD = 16 ms). Conclusions: Changes in different ECG biomarkers of ventricular repolarization display different kinetics after administration of a potent potassium channel blocker. These differences need to be taken into account when designing ventricular repolarization ECG studies. Ann Noninvasive Electrocardiol 2010;15(1):26,35 [source] Autonomic nervous system functions in children with breath-holding spells and effects of iron deficiencyACTA PAEDIATRICA, Issue 9 2005Abdülkerim Kolkiran Abstract Aim: To analyse the activity of the autonomic nervous system during breath-holding spells, we assessed the ECG changes, including ventricular repolarization parameters before and during the spell. We also analysed the effects of iron deficiency on these ECG parameters. Methods: The study group consisted of 37 children with breath-holding spells (30 cyanotic, 7 pallid) (mean age±SD: 12.9±10.8 mo). Twenty-six healthy children (mean age±SD: 14.4±8.6 mo) served as a control group. All patients and controls had standard 12-lead simultaneous surface ECG. All patients had ECG recordings during at least one severe breath-holding spell obtained by "event recorder". Traces obtained by "event recorder" were analysed in terms of mean heart rate and the frequency and duration of asystole during the spell. Results: Respiratory sinus arrhythmia on standard ECGs and asystole frequency during spells were higher in patients with pallid breath-holding spells. Patients with iron deficiency had a lower frequency of respiratory sinus arrhythmia and prolonged asystole time during the spell. There was no difference in terms of ventricular repolarization parameters (QT/QTc intervals and QT/QTc dispersions) between patients and controls and between patient subgroups (cyanotic versus pallid). Conclusion: These results confirmed the presence of autonomic dysregulation in children with breath-holding spells. Iron deficiency may have an impact on this autonomic dysregulation. Ventricular repolarization was unaffected in patients with breath-holding spells. [source] Differences in sino-atrial and atrio-ventricular function with age and sex attributable to the Scn5a+/, mutation in a murine cardiac modelACTA PHYSIOLOGICA, Issue 1 2010K. Jeevaratnam Abstract Aim:, To investigate the interacting effects of age and sex on electrocardiographic (ECG) features of Scn5a+/, mice modelling Brugada syndrome. Methods:, Recordings were performed on anaesthetized wild-type (WT) and Scn5a+/, mice and differences attributable to these risk factors statistically stratified. Results:,Scn5a+/, exerted sex-dependent effects upon sino-atrial function that only became apparent with age. RR intervals were greater in old male than in old female Scn5a+/,. Atrio-ventricular (AV) conduction was slower in young female mice, whether WT and Scn5a+/,, than the corresponding young male WT and Scn5a+/,. However, PR intervals lengthened with age in male but not in female Scn5a+/, giving the greatest PR intervals in old male Scn5a+/, compared with either old male WT or young male Scn5a+/, mice. In contrast, PR intervals were similar in old female Scn5a+/, and in old female WT. QTc was prolonged in Scn5a+/, compared with WT, and female Scn5a+/, compared with female WT. Age-dependent alterations in durations of ventricular repolarization relative to WT affected male but not female Scn5a+/,. Thus, T-wave durations were greater in old male Scn5a+/, compared with old male WT, but indistinguishable between old female Scn5a+/, and old female WT. Finally, analysis for combined interactions of genotype, age and sex demonstrated no effects on P wave and QRS durations and QTc intervals. Conclusion:, We demonstrate for the first time that age, sex and genotype exert both independent and interacting ECG effects. The latter suggest alterations in cardiac pacemaker function, atrio-ventricular conduction and ventricular repolarization greatest in ageing male Scn5a+/,. [source] Electrophysiological determinants of hypokalaemia-induced arrhythmogenicity in the guinea-pig heartACTA PHYSIOLOGICA, Issue 4 2009O. E. Osadchii Abstract Aim:, Hypokalaemia is an independent risk factor contributing to arrhythmic death in cardiac patients. In the present study, we explored the mechanisms of hypokalaemia-induced tachyarrhythmias by measuring ventricular refractoriness, spatial repolarization gradients, and ventricular conduction time in isolated, perfused guinea-pig heart preparations. Methods:, Epicardial and endocardial monophasic action potentials from distinct left ventricular (LV) and right ventricular (RV) recording sites were monitored simultaneously with volume-conducted electrocardiogram (ECG) during steady-state pacing and following a premature extrastimulus application at progressively reducing coupling stimulation intervals in normokalaemic and hypokalaemic conditions. Results:, Hypokalaemic perfusion (2.5 mm K+ for 30 min) markedly increased the inducibility of tachyarrhythmias by programmed ventricular stimulation and rapid pacing, prolonged ventricular repolarization and shortened LV epicardial and endocardial effective refractory periods, thereby increasing the critical interval for LV re-excitation. Hypokalaemia increased the RV-to-LV transepicardial repolarization gradients but had no effect on transmural dispersion of APD90 and refractoriness across the LV wall. As determined by local activation time recordings, the LV-to-RV transepicardial conduction and the LV transmural (epicardial-to-endocardial) conduction were slowed in hypokalaemic heart preparations. This change was attributed to depressed diastolic excitability as evidenced by increased ventricular pacing thresholds. Conclusion:, These findings suggest that hypokalaemia-induced arrhythmogenicity is attributed to shortened LV refractoriness, increased critical intervals for LV re-excitation, amplified RV-to-LV transepicardial repolarization gradients and slowed ventricular conduction in the guinea-pig heart. [source] Left Ventricular Function in Male Patients with Secondary HypogonadismECHOCARDIOGRAPHY, Issue 3 2007Oben Baysan M.D. Background: In addition to the effects on ventricular repolarization, testosterone could also affect left ventricular performance. The enhancement of left ventricular contractility in testosterone-deficient rats following testosterone replacement implies to the possible testosterone effect. Objectives: The aim of the current study is to reveal the alterations of left ventricular functions, if any, in secondary hypogonadal male patients. Methods: Thirty-four males with secondary hypogonadism comprised the study group. The control group consisted of 30 healthy subjects. Echocardiographic measurements including left ventricular dimensions, ejection fraction, mitral inflow, and left ventricular outflow parameters were obtained from all subjects. Tissue Doppler parameters were also measured from left ventricular lateral wall and interventricular septum. Results: Left ventricular diameters, wall thicknesses, and performance parameters were similar in both groups. Mitral inflow parameters showed a statistically insignificant difference. Pulse-wave tissue Doppler interpretation of hypogonadal and healthy subjects were similar in terms of lateral and septal basal segment Sm, Em, and Am wave velocities. Conclusions: Regarding the findings of previous studies that showed impaired myocardial contractility and lusitropy in testosterone deficient rats and our study results, further studies are needed for better understanding of testosterone's effects on human myocardium. [source] Chamber-specific effects of hypokalaemia on ventricular arrhythmogenicity in isolated, perfused guinea-pig heartEXPERIMENTAL PHYSIOLOGY, Issue 4 2009Oleg E. Osadchii Diuretic-induced hypokalaemia has been shown to promote cardiac arrhythmias in hypertensive patients. The present study was designed to determine whether hypokalaemia increases arrhythmic susceptibility of the left ventricle (LV) or the right ventricle (RV), or both. Proarrhythmic effects of hypokalaemic perfusion (2.5 mm K+ for 30 min) were assessed in isolated guinea-pig heart preparations using simultaneous recordings of volume-conducted electrocardiogram and monophasic action potentials from six ventricular epicardial sites. Effective refractory periods, ventricular fibrillation thresholds and inducibility of tachyarrhythmias by programmed electrical stimulation and tachypacing were determined at the LV and the RV epicardial stimulation sites. Hypokalaemia promoted spontaneous ventricular ectopic activity, an effect attributed to non-uniform prolongation of ventricular repolarization resulting in increased RV-to-LV transepicardial dispersion of refractoriness and action potential duration. Furthermore, hypokalaemic perfusion was associated with reduced ventricular fibrillation threshold and increased inducibility of tachyarrhythmias by programmed electrical stimulation and tachypacing as determined at the LV stimulation site. In contrast, the RV stimulation revealed no change in arrhythmic susceptibility of the RV chamber. Consistently, hypokalaemia reduced the LV effective refractory period but had no effect on the RV refractoriness. This change enabled generation of premature propagating responses by extrastimulus application at earlier time points during LV repolarization. Increased prematurity of extrastimulus-evoked propagating responses was associated with exaggerated local inhomogeneities in intraventricular conduction and action potential duration in hypokalaemic LV, thus creating a favourable stage for re-entrant tachyarrhythmias. Taken together, these findings suggest that proarrhythmic effects of hypokalaemia are mostly attributed to increased LV arrhythmogenicity in the guinea-pig heart. [source] Evidences of the gender-related differences in cardiac repolarization and the underlying mechanisms in different animal species and humanFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 1 2006Jianhua Cheng Abstract Clinical and experimental studies have shown that gender differences exist in cardiac repolarization in various animal species and human, as is evidenced by significantly longer QT, JT intervals and action potential duration in females than in males due to a reduced repolarization reserve in females. The latter is shown by the relatively greater increase in ventricular repolarization and higher incidence of torsades de pointes (TdP) in preparations from females by drugs blocking repolarizing K+ currents. These results can be modulated by gonadectomy, suggesting that gonadal steroids are important determinants of gender difference in repolarization. In human subjects, QT and JT intervals are longer in women, whereas QT dispersion and Tp-e interval (the interval from the peak to the end of T wave) are longer in men. At slow heart rates greater prolongation in QT and increase in transmural repolarization heterogeneity (i.e. increase in Tp-e) may predispose to TdP tachycardias in women. In healthy postmenopausal women, hormone replacement therapy with estrogen alone usually produced a prolongation of QT interval, while estrogen plus progesterone had no significant effects on QT interval but reduced QT dispersion. Along with these, there are still conflicting data reported. Further work is needed before the elucidation of the basis of gender differences in ventricular repolarization. [source] The Effect of Antihistamine Cetirizine on Ventricular Repolarization in Congenital Long QT SyndromeJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 7 2007ANNA-MARI HEKKALA M.D. Introduction: Many drugs are known to block cardiac potassium channels, thus prolonging QT interval and predisposing to malignant arrhythmias. Patients with congenital long QT syndrome are particularly vulnerable, but usually electrophysiological effects of drugs have not been assessed in these patients at risk. Methods: Fifteen asymptomatic patients with type 1 (LQT1), 15 patients with type 2 (LQT2) long QT syndrome, and 15 healthy volunteers took a placebo and cetirizine 10 mg. In addition, healthy volunteers took cetirizine 50 mg. The study was single-blinded and randomized. Exercise tests were performed during stable plasma concentrations. The electrocardiogram was recorded with a body surface potential mapping system (BSPM). Data were analyzed with an automated analyze program. QT intervals to the T wave apex and T wave end and their difference (Tp-e) were determined at rest and at specified heart rates during and after exercise. Results: Cetirizine did not lengthen the QT intervals at rest or during exercise and recovery in any group. It shortened Tp-e at rest in LQT1 and LQT2 patients and during exercise test in LQT1 patients, thus slightly decreasing electrocardiographic transmural dispersion of repolarization. Conclusions: Cetirizine does not adversely modify ventricular repolarization in types 1 and 2 long QT syndrome, suggesting that it might be used safely in these long QT syndrome patients. [source] Heterogeneous Regional Endocardial Repolarization is Associated with Increased Risk for Ischemia-Dependent Ventricular Fibrillation after Myocardial InfarctionJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 8 2003Michael H. Swann M.SC. Introduction: The aim of this study was to investigate whether the characteristics of endocardial ventricular repolarization are associated with differential risk for sudden death. Prolonged surface QT interval is associated with increased arrhythmic risk after myocardial infarction (MI), but the underlying mechanism of QT prolongation and its relation to lethal arrhythmias are unclear. Methods and Results: Ventricular fibrillation (VF) risk was assessed in 12 dogs 1 month after anterior MI during an exercise test coupled with brief circumflex coronary occlusion. Susceptible dogs (n = 5) developed VF during the brief ischemic episode, whereas resistant dogs did not (n = 7). Surface QT interval was measured at rest. Endocardial electroanatomic catheter maps of left ventricular repolarization were obtained in four unique regions identified by echocardiography and compared between groups. Compared to resistant dogs, susceptible dogs were characterized by prolonged surface QT intervals (240 ± 10 msec vs 222 ± 7 msec, P = 0.04). In addition, they had lower baroreflex sensitivity (9.7 ± 1.5 msec/mmHg vs 28 ± 9.8 msec/mmHg, P < 0.01) and a tachycardic response to acute ischemia suggesting higher propensity for stronger sympathetic reflexes. Surface QT interval prolongation in susceptible dogs was due to a marked heterogeneity of endocardial left ventricular repolarization (239 ± 42 msec, basal anterior wall vs 197 ± 35, lateral wall; P < 0.001). Resistant animals had no regional differences in endocardial repolarization. Conclusion: Sympathetic activation following MI not only produces adverse structural remodeling but also contributes to adverse electrophysiologic remodeling resulting in heterogeneous ventricular repolarization and in a myocardial substrate conducive to lethal reentrant arrhythmias. (J Cardiovasc Electrophysiol, Vol. 14, pp. 873-879, August 2003) [source] Arrhythmogenesis of T Wave Alternans Associated with Surface QRS Complex Alternans and the Role of Ventricular Prematurity: Observations from a Canine Model of LQT3 SyndromeJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 6 2002MASAOMI CHINUSHI M.D. Intramural TWA and Its Arrhythmogenesis.Introduction: T wave alternans (TWA) is characterized by cycle-to-cycle changes in the QT interval and/or T wave morphology. It is believed to amplify the underlying dispersion of ventricular repolarization. The aim of this study was to examine the mechanisms and arrhythmogenesis of TWA accompanied by QRS complex and/or blood pressure (BP) waveform alternans, using transmural ventricular electrogram recordings in an anthopleurin-A model of long QT syndrome. Methods and Results: The cardiac cycle length was gradually shortened by interruption of vagal stimulation, and TWA was induced in six canine hearts. Transmural unipolar electrograms were recorded with plunge needle electrodes from endocardial (Endo), mid-myocardial (Mid), and epicardial (Epi) sites, along with the surface ECG and BP. The activation-recovery interval (ARI) was measured to estimate local refractoriness. During TWA, ARI alternans was greater at the Mid than the Epi/Endo sites, and it was associated with the development of marked spatial dispersion of ventricular repolarization. As TWA increased, ventricular activation of the cycles associated with shorter QT intervals displayed delayed conduction at the Mid sites as a result of a critically longer ARI of the preceding cycle and longer QT interval, while normal conduction was preserved at the Epi site. Delayed conduction at the Mid sites manifested as surface ECG QRS and BP waveform alternans, and spontaneous ventricular tachyarrhythmias developed in absence of ventricular prematurity. In other instances, in absence of delayed conduction during TWA, ventricular premature complexes infringed on a prominent spatial dispersion of ventricular repolarization of cycles with long QT intervals and initiated ventricular tachyarrhythmia. Conclusion: TWA accompanied by QRS alternans may signal a greater ventricular electrical instability, since it is associated with intramural delayed conduction, which can initiate ventricular tachyarrhythmia without ventricular premature complexes. [source] Independent Autonomic Modulation of Sinus Node and Ventricular Myocardium in Healthy Young Men During SleepJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 10 2000PETER KOWALLIK M.D. Autonomic Modulation of Sinus Node and Ventricle. Introduction. The aim of this study was to investigate whether autonomic modulation of ventricular repolarization may spontaneousiy differ from that of the sinoatrial node. Methods and Results. Onset of P waves. QRS complexes, and the apex and end of T waves were detected heat to heat in high-resolution ECGs from nine healthy young men during the night. There were time-dependent fluctuations in the QT/RR slopes of consecutive 5-minute segments that could not he explained by the mean RR cycle length of the respective segment. Because the variahility found in QT intervals could not be explained hy either possible effects of rate dependence or hysteresis, autonomic effects were obvious. Power speetral analysis was performed for consecutive 5-minute segments of PP and QT techograms. In a given subject. trends in the time course of low-frequency (LF) and high-frequency (HF) power in PP and QT often were similar, but they were quite different at other times. The mean LF/HF ratio for QTend (0.75 ± 0.1) was different from that of PP (1.8 ± 0.2; P = 0.002), indicating differences in sympathovagal balance at the different anatomic sites. Furthermore, at a given mean heart rate, averaged QT intervals were different on a time scale of several minutes to hours. The QT/RR slope of 5-minute segments correlated significantly with the HF power of QT variability but not with that of PP variability, indicating effects of the autonomic nervous system on ventricular action potential restitution. Conclusion. These differences demonstrate that changes in sinus node automaticity are not necessarily indicative of the autonomic control of ventricular myocardium. (J Cardiavasc Electrophysiol, Vol. II, pp. 1063-1070. October 2000) [source] QT Dispersion Does Not Represent Electrocardiographic Interlead Heterogeneity of Ventricular RepolarizationJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 8 2000MAREK MALIK Ph.D. QT Dispersion and Repolarization Heterogeneity. Introduction: QT dispersion (QTd, range of QT intervals in 12 ECG leads) is thought to reflect spatial heterogeneity of ventricular refractoriness. However, QTd may be largely due to projections of the repolarization dipole rather than "nondipolar" signals. Methods and Results: Seventy-eight normal subjects (47 ± 16 years, 23 women), 68 hypertrophic cardiomyopathy patients (HCM; 38 ± 15 years. 21 women), 72 dilated cardiomyopathy patients (DCM; 48 ± 15 years, 29 women), and 81 survivors of acute myocardial infarction (AMI; 63 ± 12 years, 20 women) had digital 12-lead resting supine ECGs recorded (10 ECGs recorded in each subject and results averaged). In each ECG lead, QT interval was measured under operator review by QT Guard (GE Marquette) to obtain QTd. QTd was expressed as the range, standard deviation, and highest-to-lowest quartile difference of QT interval in all measurable leads. Singular value decomposition transferred ECGs into a minimum dimensional time orthogonal space. The first three components represented the ECG dipole; other components represented nondipolar signals. The power of the T wave nondipolar within the total components was computed to measure spatial repolarization heterogeneity (relative T wave residuum, TWR). OTd was 33.6 ± 18.3, 47.0 ± 19.3, 34.8 ± 21.2, and 57.5 ± 25.3 msec in normals, HCM, CM, and AMI, respectively (normals vs DCM: NS, other P < 0.009). TWR was 0.029%± 0.031%, 0.067%± 0.067%, 0.112%± 0.154%, and 0.186%± 0.308% in normals, HCM, DCM, and AMI (HCM vs DCM: NS. other P < 0.006), The correlations between QTd and TWR were r = -0.0446, 0.2805, -0.1531, and 0.0771 (P = 0.03 for HCM, other NS) in normals, HCM, DCM, and AMI, respectively. Conclusion: Spatial heterogeneity of ventricular repolarization exists and is measurable in 12-lead resting ECGs. It differs between different clinical groups, but the so-called QT dispersion is unrelated to it. [source] Changes in Left Ventricular Repolarization and Ion Channel Currents Following a Transient Rate Increase Superimposed on Bradycardia in Anesthetized DogsJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 6 2000MICHAEL RUBART M.D. Electrical Remodeling of the Heart due to Rate. Introduction: We previously demonstrated in dogs that a transient rate increase superimposed on bradycardia causes prolongation of ventricular refractoriness that persists for hours after resumption of bradycardia. In this study, we examined changes in membrane currents that are associated with this phenomenon. Methods and Results: The whole cell, patch clamp technique was used to record transmembrane voltages and currents, respectively, in single mid-myocardial left ventricular myocytes from dogs with 1 week of complete AV block; dogs either underwent 1 hour of left ventricular pacing at 120 beats/min or did not undergo pacing. Pacing significantly heightened mean phase 1 and peak plateau amplitudes by ,6 and ,3 mV, respectively (P < 0.02). and prolonged action potential duration at 90% repolarization from 235 ± 8 msec to 278 ± 8 msec (1 Hz; P = 0.02). Rapid pacing-induced changes in transmembrane ionic currents included (1) a more pronounced cumulative inactivation of the 4-aminopyridine-sensitive transient outward K+ current, I to over the range of physiologic frequencies, resulting from a ,30% decrease in the population of quickly reactivating channels; (2) increases in peak density of L-type Ca2+ currents, Ica.I.' by 15% to 35% between +10 and +60 mV; and (3) increases in peak density of the Ca2+ -activated chloride current, ICl.Ca' by 30% to 120% between +30 and +50 mV. Conclusion: Frequency-dependent reduction in Ito combined with enhanced ICa.I. causes an increase in net inward current that may he responsible for the observed changes in ventricular repolarization. This augmentation of net cation influx is partially antagonized by an increase in outward ICa.Cl. [source] Analysis of the Corrected QT Before the Onset of Nonsustained Ventricular Tachycardia in Patients with Hypertrophic CardiomyopathyPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 1p2 2003BARANOWSKI BARANOWSKI, R., et al.: Analysis of the Corrected QT Before the Onset of Nonsustained Ventricular Tachycardia in Patients with Hypertrophic Cardiomyopathy. This study examined ventricular repolarization before the onset of 37 episodes of nonsustained ventricular tachycardia (NSVT) in 26 untreated patients with hypertrophic cardiomyopathy (HCM). Fourteen episodes were recorded in patients with a history of cardiac arrest or patients who died suddenly during follow-up. The QT interval was measured beat-by-beat on 24-hour ambulatory electrocardiograms. Mean 24-hour, hourly QTc and QTc of the last 10 beats prior to NSVT, consisted of 4,50 cycles (mean9 ± 10), at the fastest rates of 100,175 beats/min (mean 122 ± 22) were analyzed. NSVT was more prevalent during nighttime (23 episodes), than during daytime (14 episodes,P < 0.05). No significant differences were observed between mean 24-hour, mean hourly QTc during the hour with NSVT, and QTc of the last 10 cycles prior to onset of NSVT. QTc was significantly longer in patients with a history of sudden cardiac death (SCD) or who died suddenly during follow-up than in survivors. The 24-hour QT variability was higher in nonsurvivors than in survivors ( -39 ± 6vs33 ± 6 ms, P = 0.03). Episodes of NSVT in untreated patients with hypertrophic cardiomyopathy were more frequent during the nighttime. The 24-hour QT variability was higher in nonsurvivors than in survivors. (PACE 2003; 26[Pt. II]:387,389) [source] Pro arrhythmic Effects of Ibutilide in a Canine Model of Pacing Induced CardiomyopathyPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 2 2000MING-HSIUNG HSIEH The authors developed a canine model of pacing induced cardio my apathy to study the possible mechanisms of ibutilide induced torsades de pointes (TP) in heart failure. Thirteen dogs received intravenous ibutilide after acute AV block for 60 minutes, and after implantation of a VVI pacemaker, with a rate of 270 beats/min for 2,3 weeks. Twelve-lead ECG and right and left ventricle monophasic action potentials were recorded at different right ventricle pacing cycle lengths from 600 ms to 1200 ms during the study. The results showed ibutilide could significantly prolong ventricular repolarization and increase the dispersion in a dose dependent and reverse use dependent manner. Furthermore, after ihutilide administration, cardiomyopathic dogs had a greater dispersion of ventricular repolarization, and also had higher incidences of early afterdepolarizations and spontaneous or pacing induced TP than acute AV block dogs. [source] The Time Course of New T-Wave ECG Descriptors Following Single- and Double-Dose Administration of Sotalol in Healthy SubjectsANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 1 2010Fabrice Extramiana M.D., Ph.D. Introduction: The aim of the study was to assess the time course effect of IKr blockade on ECG biomarkers of ventricular repolarization and to evaluate the accuracy of a fully automatic approach for QT duration evaluation. Methods: Twelve-lead digital ECG Holter was recorded in 38 healthy subjects (27 males, mean age = 27.4 ± 8.0 years) on baseline conditions (day 0) and after administration of 160 mg (day 1) and 320 mg (day 2) of d-l sotalol. For each 24-hour period and each subject, ECGs were extracted every 10 minutes during the 4-hour period following drug dosage. Ventricular repolarization was characterized using three biomarker categories: conventional ECG time intervals, principal component analysis (PCA) analysis on the T wave, and fully automatic biomarkers computed from a mathematical model of the T wave. Results: QT interval was significantly prolonged starting 1 hour 20 minutes after drug dosing with 160 mg and 1 hour 10 minutes after drug dosing with 320 mg. PCA ventricular repolarization parameters sotalol-induced changes were delayed (>3 hours). After sotalol dosing, the early phase of the T wave changed earlier than the late phase prolongation. Globally, the modeled surrogate QT paralleled manual QT changes. The duration of manual QT and automatic surrogate QT were strongly correlated (R2= 0.92, P < 0.001). The Bland and Altman plot revealed a nonstationary systematic bias (bias = 26.5 ms ± 1.96*SD = 16 ms). Conclusions: Changes in different ECG biomarkers of ventricular repolarization display different kinetics after administration of a potent potassium channel blocker. These differences need to be taken into account when designing ventricular repolarization ECG studies. Ann Noninvasive Electrocardiol 2010;15(1):26,35 [source] T-Wave Variability Detects Abnormalities in Ventricular Repolarization: A Prospective Study Comparing Healthy Persons and Olympic AthletesANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 3 2009Lara Heinz M.D. Background: Sudden cardiac death in athletes is more common than in the general population. Routine screening procedures are performed to identify competitors at risk. A new Holter-based parameter analyzes variation of the ventricular repolarization (TVar). The aim of this study was to evaluate differences in electrocardiogram (ECG), Echo, and Holter (H) in competitive athletes compared to a healthy control group consisting of medical students (MS). Methods: A total of 40 athletes (19 females, Olympic team, Luxembourg) and 40 MS (22 females) were examined by means of a resting ECG, treadmill exercise (TE), echocardiogram (Echo), as well as H recordings during a routine screening visit. To analyze TVar, a 20-minute H recording at rest (sampling rate 1000 per second) was performed. Moreover, heart rate variability (HRV) as well as HR turbulence (HRT) was computed. Results: No differences in demographic variables were detected. Quantification of HRV detected a significant increase in the vagal component of autonomic cardiac modulation. In contrast, no differences for HRT were found. Echo parameter demonstrated a thicker septal wall without differences of the posterior wall. TVar values were normal in range, but did differ significantly between the two groups. No correlation between TVar and echo as well as Holter parameters was detected. Conclusions: TVar was able to demonstrate significant differences in terms of alterations of ventricular activation. This might indicate an early change of myocardial repolarization representing a substrate for life-threatening arrhythmia. Larger studies on the predictive value of TVar including follow-up are necessary to confirm this preliminary finding. [source] Ionic Mechanisms and Vectorial Model of Early Repolarization Pattern in the Surface Electrocardiogram of the AthleteANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 3 2008Eduardo C. Barbosa M.D. Background: The electrocardiogram (ECG) of the athlete displays particular characteristics as a consequence of both electrophysiological and autonomic remodeling of the heart that follows continued physical training. However, doubts persist on how these changes directly interact during ventricular activation and repolarization ultimately affecting surface ECG waveforms in athletes. Objective: This article considers an in deep rationale for the electrocardiographic pattern known as early repolarization based on both electrophysiological mechanisms at cellular level and the vectorial theory of the cardiac activation. Methods: The mechanism by which the autonomic remodeling influences the cardiac electrical activation is reviewed and an insight model of the ventricular repolarization based on ionic models and the vectorial theory of the cardiac activation is proposed. Results: Considering the underlying processes related to ventricular electrical remodeling, we propose that, in athletes' heart: 1) vagal modulation increases regional electrophysiological differences in action potential phases 1 and 2 amplitudes, thus enhancing a voltage gradient between epicardial and endocardial fibers; 2) this gradient affects depolarization and repolarization timing sequences; 3) repolarization wave front starts earlier on ventricular wall and partially overcomes the end of depolarization causing an upward displacement of the J-point, ST segment elevation, and inscription of magnified T-waves amplitudes leading to characteristic surface ECG waveform patterns. Conclusions: In athletes, the association between epicardial to endocardial electrophysiological differences and early repolarization ECG pattern can be demonstrated by the vectorial theory of the ventricular activation and repolarization. [source] Electrocardiographic Alterations during Hyperinsulinemic Hypoglycemia in Healthy SubjectsANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 2 2008Tomi Laitinen M.D. Background: We evaluated the arrhythmogenic potential of hypoglycemia by studying electrocardiographic (ECG) changes in response to hyperinsulinemic hypoglycemia and associated sympathoadrenal counterregulatory responses in healthy subjects. Methods: The study population consisted of 18 subjects, aged 30,40 years. Five-minute ECG recordings and blood samplings were performed at baseline and during the euglycemic and hypoglycemic hyperinsulinemic clamp studies. PR, QT, and QTc intervals of electrocardiogram and ECG morphology were assessed from signal-averaged ECG. Results: Although cardiac beat interval remained unchanged, PR interval decreased (P < 0.01) and QTc interval (P < 0.001) increased in response to hyperinsulinemic hypoglycemia. Concomitant morphological alterations consisted of slight increases in R-wave amplitude and area (P < 0.01 for both), significant decreases in T-wave amplitude and area (P < 0.001 for both), and moderate ST depression (P < 0.001). Counterregulatory norepinephrine response correlated with amplification of the R wave (r =,0.620, P < 0.05) and epinephrine response correlated with flattening of the T wave (r =,0.508, P < 0.05). Conclusions: Hyperinsulinemic hypoglycemia with consequent sympathetic humoral activation is associated with several ECG alterations in atrioventricular conduction, ventricular depolarization, and ventricular repolarization. Such alterations in cardiac electrical function may be of importance in provoking severe arrhythmias and "dead-in-bed" syndrome in diabetic patients with unrecognized hypoglycemic episodes. [source] Differences between Ventricular Repolarization in Men and Women: Description, Mechanism and ImplicationsANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 4 2003Borys Surawicz M.D., M.A.C.C. The purpose of this review article is to discuss the differences between ventricular repolarization in males and females in terms of morphology, possible mechanism, and practical significance. The interest in the subject increased when it became known that in comparison to men, women have a higher incidence of torsade de pointes (tdp) and a greater lengthening of QT-interval after administration of class III antiarrhythmic drugs. Before puberty, the QT intervals and the patterns of ventricular repolarization in boys and girls are similar. At puberty, in boys the QT interval shortens, and a typical male pattern of ventricular repolarization develops. This pattern is characterized by a higher amplitude of the J-point, a shorter and steeper ST segment course, a steeper ascent, and a higher amplitude of the T wave. This pattern is prevalent in >90% of young males. With increasing age the prevalence of the male pattern in males declines gradually and drops to 14% in the oldest age group. The rise and fall of the prevalence of the male pattern appears to parallel the rise and decline of testosterone in males. The female pattern of ventricular repolarization is prevalent in about 80% of females in all age groups. The hormonal effects on ventricular repolarization have been studied in normal and castrated rabbits of both sexes. The available evidence indicates that the females have greater divergence of L calcium current among different layers of the myocardium and a lower density of the repolarizing Kr and Ks currents. The clinical significance of the repolarization differences among genders remains to be determined. Of particular interest is the question whether the males with female pattern are at the same risk of tdp as the females or whether the females with male pattern are at lower risk of tdp than the females with female pattern. [source] Electrocardiographic Quantitation of Heterogeneity of Ventricular RepolarizationANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 1 2000Peter M. Okin M.D. Background:QT interval dispersion (QTd) measured from the surface ECG has emerged as the most common noninvasive method for assessing heterogeneity of ventricular repolarization. Although QTd correlates with dispersion of monophasic action potential duration at 90% repolarization and with dispersion of recovery time recorded from the epicardium, total T-wave area, representing a summation of vectors during this time interval, has been shown to have the highest correlation with these invasive measures of dispersion of repolarization. However, recent clinical studies suggest that the ratio of the second to first eigenvalues of the spatial T-wave vector using principal component analysis (PCA ratio) may more accurately reflect heterogeneity of ventricular repolarization. Methods:To better characterize the ECG correlates of surface ECG measures of heterogeneity of ventricular repolarization and to establish normal values of these criteria using an automated measurement method, the relations of QRS onset to T-wave offset (QTod) and to T-wave peak (QTpd) dispersion and the PCA ratio to T-wave area and amplitude, heart rate, QRS axis and duration, and the QTo interval were examined in 163 asymptomatic subjects with normal resting ECGs and normal left ventricular mass and function. QTod and QTpd were measured by computer from digitized ECGs as the difference between the maximum and minimum QTo and QTp intervals, respectively. Results:In univariate analyses, a significant correlation was found between the sum of the T-wave area and the PCA ratio (R =,0.46, P < 0.001), but there was no significant correlation of the sum of T-wave area with QTod (R = 0.11, P = NS) or QTpd (R=0.09, P = NS). There were only modest correlations between QTod and QTpd (R = 0.45) and between the PCA ratio and QTod (R = 0.29) and QTpd (R = 0.49) (each P < 0.001). In stepwise multivariate linear regression analyses, the PCA ratio was significantly related to the sum of T-wave area, T-wave amplitude in aVL, and to female gender (overall R = 0.54, P < 0.001), QTod correlated only with the maximum QTo0 interval (R = 0.39, P < 0.001), and QTpd was related to heart rate and QRS axis (overall R = 0.36, P <0.001). In addition, the normal interlead dispersion of repolarization as measured by QTod was significantly greater than dispersion measured by QTod (23.5 ± 11.5 ms vs 18.3 ± 11.2 ms, P < 0.001). Conclusions: These findings provide new information on ECG measures of heterogeneity of repolarization in normal subjects, with a significantly higher intrinsic variability of Q to T-peak than Q to T-offset dispersion and only modest correlation between these wo measures. The independent relation of the PCA ratio to the sum of T-wave area suggests that the PCA ratio may be a more accurate surface ECG reflection of the heterogeneity of ventricular repolarizat on. A.N.E. 2000;5(1):79,87 [source] Influence of exposure to electromagnetic field on the cardiovascular systemAUTONOMIC & AUTACOID PHARMACOLOGY, Issue 1 2005J. H. Jeong Summary 1 We examined whether extremely low frequency electromagnetic fields (ELF-EMF) affect the basal level of cardiovascular parameters and influence of drugs acting on the sympathetic nervous system. 2 Male rats were exposed to sham control and EMF (60 Hz, 20 G) for 1 (MF-1) or 5 days (MF-5). We evaluated the alterations of blood pressure (BP), pulse pressure (PP), heart rate (HR), and the PR interval, QRS interval and QT interval on the electrocardiogram and dysrhythmic ratio in basal level and dysrhythmia induced by , -adrenoceptor agonists. 3 In terms of the basal levels, there were no statistically significant differences among control, MF-1 and MF-5 in PR interval, QRS interval, mean BP, HR and PP. However, the QT interval, representing ventricular repolarization, was significantly reduced by MF-1 (P < 0.05). 4 (,)-Dobutamine (,1 -adrenoceptor-selective agonist)-induced tachycardia was significantly suppressed by ELF-EMF exposure in MF-1 for the increase in HR (,HR), the decrease in QRS interval (,QRS) and the decrease in QT (,QT) interval. Adrenaline (nonselective , -receptor agonist)-induced dysrhythmia was also significantly suppressed by ELF-EMF in MF-1 for the number of missing beats, the dysrhythmic ratio, and the increase in BP and PP. 5 These results indicated that 1-day exposure to ELF-EMF (60 Hz, 20 G) could suppress the increase in HR by affecting ventricular repolarization and may have a down-regulatory effect on responses of the cardiovascular system induced by sympathetic agonists. [source] Dog left ventricular midmyocardial myocytes for assessment of drug-induced delayed repolarization: short-term variability and proarrhythmic potentialBRITISH JOURNAL OF PHARMACOLOGY, Issue 1 2010Najah Abi-Gerges Background and purpose:, Evaluation of the potential for delayed ventricular repolarization and proarrhythmia by new drugs is essential. We investigated if dog left ventricular midmyocardial myocytes (LVMMs) that can be used as a preclinical model to assess drug effects on action potential duration (APD) and whether in these cells, short-term variability (STV) or triangulation could predict proarrhythmic potential. Experimental approach:, Beagle LVMMs and Purkinje fibres (PFs) were used to record APs. Effects of six reference drugs were assessed on APD at 50% (APD50) and 90% (APD90) of repolarization, STV(APD), triangulation (ratio APD90/APD50) and incidence of early afterdepolarizations (EADs) at 1 and 0.5 Hz. Key results:, LVMMs provided stable recordings of AP, which were not affected by four sequential additions of dimethyl sulphoxide. Effects of dofetilide, d-sotalol, cisapride, pinacidil and diltiazem, but not of terfenadine, on APD in LVMMs were found to be comparable with those recorded in PFs. LVMMs, but not PFs, exhibited a proarrhythmic response to IKr blockers. Incidence of EADs was not related to differences in AP prolongation or triangulation, but corresponded to beat-to-beat variability of repolarization, here quantified as STV of APD. Conclusions and implications:, LVMMs provide a suitable preclinical model to assess the effects of new drugs on APD and also yield additional information about putative indicators of proarrhythmia that add value to an integrated QT/TdP risk assessment. Our findings support the concept that increased STV(APD) may predict drug-induced proarrhythmia. This article is part of a themed section on QT safety. To view this issue visit http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2010 [source] |