Formation of a border ischemic zone depends on plasma potassium concentration.

Extracellular potassium concentration might modify electrophysiological properties in the border zone of ischemic myocardium. We evaluated the depolarization and repolarization characteristics across the ischemic-normal border under [K+] variation. Sixty-four-lead epicardial mapping was performed in 26 rats ([K+] 2.3-6.4 mM) in a model of acute ischemia/reperfusion. The animals with [K+] < 4.7 mM (low-normal potassium) had an ischemic zone with ST-segment elevation and activation delay, a border zone with ST-segment elevation and no activation delay, and a normal zone without electrophysiological abnormalities. The animals with [K+] >4.7 mM (normal-high potassium) had only the ischemic and normal zones and no transitional area. Activation-repolarization intervals and local conduction velocities were inversely associated with [K+] in linear regression analysis with adjustment for the zone of myocardium. The reperfusion extrasystolic burden (ESB) was greater in the low-normal as compared to normal-high potassium animals. Ventricular tachycardia/fibrillation incidence did not differ between the groups. In patch-clamp experiments, hypoxia shortened action potential duration at 5.4 mM but not at 1.3 mM of [K+]. IK(ATP) current was lower at 1.3 mM than at 5.4 mM of [K+]. We conclude that the border zone formation in low-normal [K+] was associated with attenuation of IK(ATP) response to hypoxia and increased reperfusion ESB.

Action potential morphology affects T-wave symmetry (simulation study).

BACKGROUND: Assessing T-wave symmetry in addition to QT subintervals measurements can provide novel independent data about ventricular repolarization abnormalities linked with arrhythmogenesis. However, the causes of the changes of T-wave symmetry are not completely understood. In silico studies showed that the more symmetrical T-waves were associated with shorter action potential duration (APD) and larger dispersion of ventricular repolarization (DOR). The aim of present simulation was to study the association between T-wave symmetry and action potential (AP) shape. METHODS: ECGs were simulated using a cellular automata model shaped as a ventricular wall segment, and two biophysically-detailed models of ventricular AP - the rabbit and the human. The symmetry ratio (SR) was calculated as a T-wave onset-peak to peak-end area ratio. The individual and combined effects of APD, DOR and AP shape on SR were simulated. To study the effect of AP shape, different APs from triangulated to rectangular were simulated. RESULTS: The simulations showed that AP shape along with APD and DOR contributes much to T-wave symmetry. APs with a flat phase 3 (triangulated) produced asymmetrical T-waves (SR ≥ 1.5) in all simulations, except the shortest APD range. APs with a rapid phase 3 (rectangular) were associated with more symmetrical T-waves (SR ≤ =1) both at the short and the long APDs. CONCLUSION: SR marker in combination with the standard ECG parameters (QT interval, Tpeak-Tend interval) may be useful to identify the proarrhythmic triangulated AP shape.

Terminal T-wave inversion predicts reperfusion tachyarrhythmias in STEMI.

INTRODUCTION: A reliable electrocardiographic predictor of ventricular fibrillation (VF) in patients with ST elevation myocardial infarction (STEMI) is lacking so far. Previous experimental/simulation study suggested a terminal T-wave inversion (TTWI) in ischemia-related ECG leads corresponding to anterior infarct localization as an independent predictor of reperfusion VF (rVF). This T-wave characteristic has never been tested as a rVF predictor in clinical settings. The aim of this study was to test if terminal T-wave inversion (TTWI) at admission ECG (before reperfusion) can serve as a predictor of ventricular fibrillation during reperfusion (rVF) in patients with anterior STEMI undergoing primary PCI. METHODS AND RESULTS: Study population included consecutive patients with anterior infarct localization admitted for primary PCI (n = 181, age 65 [57; 76] years, 66% male). Of those, 14 patients had rVF (rVF group, age 59 [47; 76] years, 64% male) and patients without rVF comprised the No-rVF group (n = 167, age 65 [57; 76] years, 66% male). Association of TTWI with rVF was analyzed using logistic regression analysis adjusted for relevant clinical and electrocardiographic covariates. The prevalence of TTWI in rVF group was 62% comparing to 23% in the No-rVF group, p = 0.005. TTWI was associated with increased risk of rVF (OR 5.51; 95% CI 1.70-17.89; p = 0.004) and remained a significant predictor after adjustment for age, gender, history of MI prior to index admission, VF before reperfusion, Tpeak-Tend, maximal ST elevation, and QRS duration (OR 23.49; 95% CI 3.14-175.91; p = 0.002). CONCLUSIONS: The terminal T-wave inversion in anterior leads before PCI independently predicted rVF in patients with anterior MI thus confirming the previous experimental/simulation findings.

Dispersion of ventricular repolarization: Temporal and spatial.

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

ECG markers of local but not global increase in dispersion of ventricular repolarization (simulation study).

BACKGROUND: An increase in local dispersion of repolarization (DOR) may contribute more to arrhythmogenesis as compared to changes of global DOR. The aim of this simulation study was to find ECG markers of local increase in DOR in conditions where global DOR remains normal. METHODS: In the framework of van Oosterom and Oostendorp ECGSIM model, the local DOR was increased in 10 different ventricular locations by (1) action potential duration (APD) shortening/lengthening both on epi- and endocardium, (2) epicardial APD shortening, and (3) endocardial APD shortening. The simulation cases where the increase in local DOR was accompanied by increase in global DOR were excluded from consideration. T-wave parameters were analyzed in the simulated precordial and anatomically ordered limb leads. RESULTS: The increase in local DOR resulted in increased lead-to­lead differences in Tpeak and Tend instants in 28 out of 32 simulated scenarios, and in an increased dispersion of Tpeak-Tend interval throughout 12 standard leads in 8 out of 32 simulated scenarios. In all simulations, the global DOR measured as a difference between earliest and latest repolarization times and standard APD deviation was the same. CONCLUSIONS: The local increase in DOR was expressed in increased lead-to­lead differences in Tpeak and Tend instants between adjacent anatomically ordered standard leads (aVL, I, aVR(-), II, aVF, III, and V1-V6), even if global DOR, Tpeak-Tend interval and Tpeak-Tend dispersion were within a normal range.

Multi-lead vs single-lead Tpeak -T end interval measurements for prediction of reperfusion ventricular tachyarrhythmias.

INTRODUCTION: Electrocardiographic Tpeak -Tend interval (Tp-Te) is a promising marker for the prediction of ventricular tachycardia and/or ventricular fibrillation (VT/VF). The study was aimed to compare single-lead vs multilead Tp-Te variables as VT/VF predictors in experimental ischemia/reperfusion model. METHODS AND RESULTS: Computer simulations were done using the ECGSIM model with an ischemic region set in anterior left ventricular apex. In 18 anesthetized cats, myocardial ischemia was induced by 30-minute ligation of left anterior descending coronary artery followed by reperfusion. Body surface ECGs in limb leads and modified precordial leads were recorded. Tp-Te was detected automatically in individual leads with a custom-designed parametric algorithm. Tp-Te dispersion and total Tp-Te were calculated as a difference between the maximal and minimal value of individual Tp-Te(s) and an interval between the earliest Tpeak and the latest Tend throughout all leads, respectively. Simulations showed that the increase of local, but not total, dispersion of repolarization characteristic for ischemic damage led to nonuniform shortening of T-peak times across 12 standard leads, which in turn resulted in the increase of single-lead Tp-Te(s), total Tp-Te and Tp-Te dispersion. Animals experienced VT/VF showed increased Tp-Te dispersion and total Tp-Te during reperfusion. In univariate logistic regression analysis, only the Tp-Te dispersion at the beginning of reperfusion was associated with the VT/VF incidence. According to ROC curve analysis, the optimal cut-off value of the Tp-Te dispersion was 17 ms (sensitivity 0.71, specificity 0.80). CONCLUSIONS: The reperfusion VT/VFs were independently predicted by increased Tp-Te dispersion, which suggests the importance of multi-lead evaluation of Tp-Te intervals.

Repolarization in perfused myocardium predicts reperfusion ventricular tachyarrhythmias.

BACKGROUND: Aim of the study was to find out which myocardial repolarization parameters predict reperfusion ventricular tachycardia and fibrillation (VT/VF) and determine how these parameters express in ECG. METHODS: Coronary occlusion and reperfusion (30/30min) was induced in 24 cats. Local activation and end of repolarization times (RT) were measured in 88 intramyocardial leads. Computer simulations of precordial electrograms were performed. RESULTS: Reperfusion VT/VF developed in 10 animals. Arrhythmia-susceptible animals had longer RTs in perfused areas [183(177;202) vs 154(140;170) ms in susceptible and resistant animals, respectively, P<0.05]. In logistic regression analysis, VT/VFs were associated with prolonged RTs in the perfused area (OR 1.068; 95% CI 1.012-1.128; P=0.017). Simulations demonstrated that prolonged repolarization in the perfused/border zone caused precordial terminal T-wave inversion. CONCLUSIONS: The reperfusion VT/VFs were independently predicted by the longer RT in the perfused zone, which was reflected in the terminal negative phase of the electrocardiographic T-wave.

Effect of action potential duration on Tpeak-Tend interval, T-wave area and T-wave amplitude as indices of dispersion of repolarization: Theoretical and simulation study in the rabbit heart.

BACKGROUND: The aim of the study was to differentiate the effect of dispersion of repolarization (DOR) and action potential duration (APD) on T-wave parameters being considered as indices of DOR, namely, Tpeak-Tend interval, T-wave amplitude and T-wave area. METHODS: T-wave was simulated in a wide physiological range of DOR and APD using a realistic rabbit model based on experimental data. A simplified mathematical formulation of T-wave formation was conducted. RESULTS: Both the simulations and the mathematical formulation showed that Tpeak-Tend interval and T-wave area are linearly proportional to DOR irrespectively of APD range, while T-wave amplitude is non-linearly proportional to DOR and inversely proportional to the minimal repolarization time, or minimal APD value. CONCLUSION: Tpeak-Tend interval and T-wave area are the most accurate DOR indices independent of APD. T-wave amplitude can be considered as an index of DOR when the level of APD is taken into account.

The Role of Transmural Repolarization Gradient in the Inversion of Cardiac Electric Field: Model Study of ECG in Hypothermia.

BACKGROUND: The changes in ventricular repolarization gradients lead to significant alterations of the electrocardiographic body surface T waves up to the T wave inversion. However, the contribution of a specific gradient remains to be elucidated. The objective of the present investigation was to study the role of the transmural repolarization gradient in the inversion of the body surface T wave with a mathematical model of the hypothermia-induced changes of ventricular repolarization. METHODS: By means of mathematical simulation, we set the hypothermic action potential duration (APD) distribution on the rabbit ventricular epicardium as it was previously experimentally documented. Then the parameters of the body surface potential distribution were tested with the introduction of different scenarios of the endocardial and epicardial APD behavior in hypothermia resulting in the unchanged, reversed or enlarged transmural repolarization gradient. RESULTS: The reversal of epicardial repolarization gradients (apicobasal, anterior-posterior and interventricular) caused the inversion of the T waves regardless of the direction of the transmural repolarization gradient. However, the most realistic body surface potentials were obtained when the endocardial APDs were not changed under hypothermia while the epicardial APDs prolonged. This produced the reversed and increased transmural repolarization gradient in absolute magnitude. The body surface potentials simulated under the unchanged transmural gradient were reduced in comparison to those simulated under the reversed transmural gradient. CONCLUSIONS: The simulations demonstrated that the transmural repolarization gradient did not play a crucial role in the cardiac electric field inversion under hypothermia, but its magnitude and direction contribute to the T wave amplitude.

Action potential duration gradients in the heart ventricles and the cardiac electric field during ventricular repolarization (a model study).

BACKGROUND: We simulated contributions of transmural, apicobasal, anteroposterior and interventricular action potential duration (APD) gradients to the body surface potential distribution (BSPD) with constant or varied magnitudes of the transmural and apicobasal gradients. METHODS: Simulations were done in the framework of the discrete computer model of the rabbit heart ventricles on the basis of realistic activation sequence and APDs. The APD gradients were set constant at 20 ms or varied in the range of ±80 ms. RESULTS: The apicobasal, transmural and interventricular APD gradients of 20 ms produced similar BSPDs, whereas the BSPD inversion was caused by the inverted apicobasal or transmural 80 ms gradients. The transmural APD gradient produced transversal and mainly apicobasal T-wave vectors due to wall curvature and cancellation effects. The "normal" transversal and apicobasal repolarization gradients were decreased and increased by activation sequence, respectively. CONCLUSION: The different APD gradients contributed consistently to the development of BSPD.

Functional role of myocardial electrical remodeling in diabetic rabbits.

The objective of the study was to investigate the role of electrical remodeling of the ventricular myocardium in hemodynamic impairment and the development of arrhythmogenic substrate. Experiments were conducted with 11 healthy and 12 diabetic (alloxan model, 4 weeks) rabbits. Left ventricular pressure was monitored and unipolar electrograms were recorded from 64 epicardial leads. Aortic banding was used to provoke arrhythmia. The diabetic rabbits had prolonged QTc, with activation-recovery intervals (surrogates for repolarization durations) being relatively short on the left ventricular base and long on the anterior apical portions of both ventricles (P < 0.05). In the diabetic rabbits, a negative correlation (-0.726 to -0.817) was observed between dP/dt(max), dP/dt(min), and repolarization dispersions. Under conditions of systolic overload (5 min), tachyarrhythmias were equally rare and the QTc and activation-recovery intervals were shortened in both groups (P < 0.05), whereas QRS was prolonged in the diabetic rabbits only. The repolarization shortening was more pronounced on the apex, which led to the development of apicobasal and interventricular end of repolarization gradients in the healthy animals, and to the flattening of the repolarization profile in the diabetic group. Thus, the diabetes-related pattern of ventricular repolarization was associated with inotropic and lusitropic impairment of the cardiac pump function.

What does the T(peak)-T(end) interval reflect? An experimental and model study.

BACKGROUND: It is unclear whether the Tpeak-Tend interval is an index of the transmural or the total dispersion of repolarization. METHODS: We examined the Tpeak-Tend interval using a computer model of the rabbit heart ventricles based on experimentally measured transmural, apicobasal, and interventricular gradients of action potential duration. RESULTS: Experimentally measured activation-recovery intervals increased from apex to base, from the left ventricle to the right ventricle, and in the apical portion of the left ventricle from epicardium to endocardium and from the right side of septum to the left side. The simulated Tpeak corresponded to the earliest end of repolarization, whereas the Tend corresponded to the latest end of repolarization. The different components of the global repolarization dispersion were discerned by simulation. CONCLUSIONS: The Tpeak-Tend interval corresponds to the global dispersion of repolarization with distinct contributions of the apicobasal and transmural action potential duration gradients and apicobasal difference in activation times.