Activation-recovery Intervals Research Articles

Effects of Bepridil Versus E-4031 on Transmural Ventricular Repolarization and Inducibility of Ventricular Tachyarrhythmias in the Dog

Bepridil (a multiple channel blocker) may markedly prolong the QT interval and induce polymorphic ventricular tachyarrhythmias (VTA). We compared the transmural ventricular repolarization characteristics and inducibility of polymorphic VTA after administration of bepridil versus the pure I(Kr) blocker, E-4031, each administered to five open-chest dogs. We used plunge needle electrode to record transmural left ventricular (LV) repolarization and activation-recovery interval (ARI) to estimate local repolarization. The correlation between paced cycle length and ARI was separately examined in the LV endocardium, mid-myocardium (Mid), and epicardium. Attempts to induce VTA were made during bradycardia and sympathetic stimulation. Bepridil and E-4031 prolonged QT interval and ARI in all LV layers, though the magnitude of prolongation was greatest in Mid, increasing the transmural ARI dispersion, particularly during bradycardia. Compared with E-4031, bepridil caused mild, reverse use-dependent changes in ventricular repolarization, and less ARI dispersion than E-4031 during slow ventricular pacing. Both drugs increased ARI(max) and cycle length at 50% of ARI(max), though the changes were smaller after bepridil than after E-4031 administration. Bradycardia after the administration of each drug induced no VTA; however, sympathetic stimulation induced sustained polymorphic VTA in two of five dogs treated with E-4031 versus no dog treated with bepridil. Unlike the pure I(kr) blocker, E-4031, bepridil exhibited weak properties of reverse use-dependency and protected against sympathetic stimulation-induced VTA. It may be an effective supplemental treatment for recipients of implantable cardioverter defibrillator.

Effects on electricalrestitution of given esmolol during cardiopulmonary resuscitation in a swine ventricularfibrillation model

：Objective To investigatethe effect on electrical restitution of β1-adrenergic receptor antagonist esmolol administered duringcardiopulmonary resuscitation in the porcine ventricular fibrillation model. MethodVentricular fibrillation untreated for four minutes was induced by dynamic steady statepacing protocol in 40 healthy male pigs, in which local unipolar electrograms wererecorded using one 10-electrode catheter that was sutured to the left ventrieularepicarditan. During CPR, animals were randomized into two groups to receive saline asplacebo or esmolol after two standards doses of epinephrine. At postresuscitation 2-hour,six pigs were randomly selected from each group and the second VF induction was performed.Local activation-recovery intervals (ARI) restitutions and the VF inducibility betweencontrol group and esmolol group were compared. Western blotting was performed to determinecardiac ryanodine receptor (RyR2) protein expression, and their phosphorylation status.Results No sig-nificant differences were observed at the restoration of spontaneouscirculation between two groups. Higher postre-suseitation 2-hour survival rate wasobserved in the esmolol group. Esmolol significantly flattened ARI restitution slope,lessened regional difference of ARI restitution, decreased the VF inducibility, andalleviated RyR2 hyper-phosphorylation. Conclusions Esmolol given during CPR significantlyimproved postresuscitation 2-hour survival rate. Its effects on modulating electricalrestitution property and intracellular calcium handling make up the most important reasonswhy β1-blockadesignificantly reduced the onset and maintenance of VF. Key words: Veutricularfibrillation; Action potentials; Restitution property; Cardiac ryanodinereceptor; Beta-adrenergic receptor

Cardiac and Electrophysiological Effects of Primary and Refined Extracts fromLeonurus cardiacaL. (Ph.Eur.)

Although several antiarrhythmic drugs of chemical origin are in clinical use since decades, their application is often limited by their adverse effects and especially by their inherited proarrhythmic risk, which can lead to a significantly increased mortality in patients receiving these compounds. On the other hand, aqueous extracts from the aerial parts of the European Lamiaceae Leonurus cardiaca (Ph.Eur.) have been used for centuries as a remedy against tachyarrhythmia and other cardiac disorders. Nevertheless, a scientific basis for the claim of direct cardiac electrophysiological, antiarrhythmic, or functional effects of Leonurus cardiacae herba (LCH) preparations has not been established until now. In order to enrich the active constituents from the primary extract which was tested as the most cardioactive, namely the aqueous Soxhlet extract, and to eliminate undesired substances such as the dichloromethanic fraction or potassium, a bioassay guided fractionation procedure was applied, resulting in the development of a Leonurus cardiaca refined extract (LCRE) which was characterised together with Leonurus crude extracts by a newly developed gradient elution HPLC fingerprint analysis for separation and quantification of six major phenolics as well as by qNMR for determining the stachydrine content. This refined extract was applied intracoronarily in isolated rabbit hearts perfused according to the Langendorff technique. Mapping experiments with 256 electrodes on the heart surface showed a reduction of left ventricular pressure and an increase of relative coronary flow at concentrations of 1.0 and 2.0 mg/mL LCRE. Furthermore, the PQ-interval was prolonged and both the basic cycle length and the activation recovery interval increased. In addition, voltage-clamp measurements were performed on the following cell models in order to characterise the electrophysiological profile of LCRE: neonatal rat ventricular cardiomyocytes to investigate the effect on I(Na) and I(Ca.L), sinoatrial node cells and ventricular myocytes isolated from adult guinea pigs to test effects on I(f) and action potential (AP) duration, as well as HERG-transfected HEK 293 cells to analyse the influence on the I (K.r). In these voltage clamp experiments LCRE exerted a calcium-antagonistic activity by I(Ca.L) blockade, reduced the repolarising current I(K.r), and prolonged the AP-duration, while I(Na) was not affected. Although LCRE displayed only weak effects on the I(f) amplitude and voltage dependence, it significantly prolonged the activation time constant of I(f). Thus, LCRE acts on multiple electrophysiological targets, specifically I(Ca.L), I(K.r), and I(f), observed both at whole organ and single cell level.

Right-to-Left Ventricular Diastolic Delay in Chronic Thromboembolic Pulmonary Hypertension Is Associated With Activation Delay and Action Potential Prolongation in Right Ventricle

Delayed left ventricle (LV)-to-right ventricle (RV) peak shortening results in cardiac output reduction in patients with chronic thromboembolic hypertension (CTEPH) and other types of pulmonary arterial hypertension. Why the synchrony between LV and RV is lost is unknown. We hypothesized that RV electrophysiological remodeling, notably, conduction slowing and action potential prolongation, contribute to this loss in synchrony. We conducted epicardial mapping during pulmonary endarterectomy in 26 patients with CTEPH and compared these findings with clinical, hemodynamic, and echocardiographic variables. We consecutively placed a multielectrode grid on the epicardium of the RV free wall and LV lateral wall. These regions corresponded to RV and LV areas where echocardiographic Doppler sample volumes were placed to measure RV-to-LV diastolic interventricular delay. RV and LV epicardial action potential duration was assessed by measuring activation-recovery interval. Onset of diastolic relaxation of RV free wall with respect to LV lateral wall (diastolic interventricular delay) was delayed by 38+/-31 ms in patients with CTEPH versus -12+/-13 ms in control subjects (P<0.001), because, in patients with CTEPH, RV completed electric activation later than LV (65+/-20 versus 44+/-7 ms, P<0.001) and epicardial action potential duration, as assessed by activation-recovery interval measurement, was longer in RV free wall than in LV lateral wall (253+/-29 versus 240+/-22 ms, P<0.001). Additive effects of electrophysiological changes in RV, notably, conduction slowing and action potential prolongation, assessed by epicardial activation-recovery interval, contribute to diastolic interventricular delay in patients with CTEPH.

Effect and mechanism of esmolol given during cardiopulmonary resuscitation in a porcine ventricular fibrillation model

Objectives The aim of the study was to investigate the effect on calcium cycling protein and electrical restitution of β 1-adrenergic receptor antagonist esmolol administered during cardiopulmonary resuscitation in the porcine ventricular fibrillation model. Methods Ventricular fibrillation untreated for four minutes was induced by dynamic steady state pacing protocol in 40 healthy male pigs, in which local unipolar electrograms were recorded using one 10-electrode catheter that was sutured to the left ventricular epicardium. During CPR, animals were randomized into two groups to receive saline as placebo or esmolol after two standard doses of epinephrine. At post-resuscitation 2-h, six pigs were randomly selected from each group and the second VF induction was performed. Local activation-recovery intervals (ARI) restitutions and the VF inducibility between control group and esmolol group were compared. Western blotting was performed to determine expression of Ca 2+/calmodulin-dependent protein kinase IIδ(CaMKIIδ) and cardiac ryanodine receptor (RyR2) protein, and their phosphorylation status. Results Injection of esmolol combined with epinephrine during CPR significantly decreased recurrent rate of ventricular fibrillation during 2-h post-resuscitation, meanwhile it has no adverse affect on the restore of spontaneous circulation. Esmolol significantly flattened ARI restitution slope, lessened regional difference of ARI restitution, decreased the VF inducibility, and alleviated CaMKIIδ hyper-activation and RyR2 hyper-phosphorylation. Conclusions Esmolol given during CPR has significant effects on modulating electrical restitution property and intracellular calcium handling, which contributes the most important reasons why β 1-blockade significantly reduced the onset and maintenance of VF.

High-Density Substrate Mapping in Brugada Syndrome

Two principal mechanisms are thought to be responsible for Brugada syndrome (BS): (1) right ventricular (RV) conduction delay and (2) RV subepicardial action potential shortening. This in vivo high-density mapping study evaluated the conduction and repolarization properties of the RV in BS subjects. A noncontact mapping array was positioned in the RV of 18 BS patients and 20 controls. Using a standard S(1)-S(2) protocol, restitution curves of local activation time and activation recovery interval were constructed to determine local maximal restitution slopes. Significant regional conduction delays in the anterolateral free wall of the RV outflow tract of BS patients were identified. The mean increase in delay was 3-fold greater in this region than in control (P=0<0.001). Local activation gradient was also maximally reduced in this area: 0.33+/-0.1 (mean+/-SD) mm/ms in BS patients versus 0.51+/-0.15 mm/ms in controls (P<0.0005). The uniformity of wavefront propagation as measured by the square of the correlation coefficient, r(2), was greater in BS patients versus controls (0.94+/-0.04 versus 0.89+/-0.09 [mean+/-SD]; P<0.05). The odds ratio of BS hearts having any RV segment with maximal restitution slope >1 was 3.86 versus controls. Five episodes of provoked ventricular tachycardia arose from wave breaks originating from RV outflow tract slow-conduction zones in 5 BS patients. Marked regional endocardial conduction delay and heterogeneities in repolarization exist in BS. Wave break in areas of maximal conduction delay appears to be critical in the initiation and maintenance of ventricular tachycardia. These data indicate that further studies of mapping BS to identify slow-conduction zones should be considered to determine their role in spontaneous ventricular arrhythmias.

Transmural Mapping of Myocardial Refractoriness and Endocardial Dispersion of Repolarization in an Ovine Model of Chronic Myocardial Infarction

Myocardial refractoriness and repolarization is an important electrophysiological property that, when altered, increases the risk of arrhythmogenesis. These electrophysiological changes associated with chronic myocardial infarction (MI) have not been studied in detail. We assessed the influence of left ventricular (LV) scarring on local refractoriness, repolarization, and electrogram characteristics. MI was induced in five sheep by percutaneous left anterior descending artery occlusion for 3 hours. Mapping was performed at 19 +/- 6 weeks post-MI. A total of 20 quadripolar transmural needles were deployed at thoracotomy in the LV within and surrounding scar. Bipolar pacing was performed from each needle to assess the effective refractory period (ERP) of the subendocardium and subepicardium. The activation (AT) and repolarization (RT) times, and modified activation recovery interval (ARI(m)) were determined from endocardial unipolar electrograms recorded in sinus rhythm simultaneously from all needles. Scarring was quantified histologically and compared with electrophysiological characteristics. Increased scarring corresponded with increased ERP (P < 0.01), decreased subendocardial electrogram amplitude (P < 0.001), and slope (P < 0.001). ERP did not differ between endocardium and epicardium (P > 0.05). The ARI(m) and RT were prolonged during early myocardial activation (P < 0.001). After adjusting for AT, the RT and ARI(m) were prolonged in areas of scarring (P < 0.001). After adjusting for electrogram amplitude, the ARI(m) was prolonged in dense scar (P < 0.05). We confirmed histologically that scarring contributes to prolongation of repolarization, increased refractoriness, and reductions in conduction and voltage post-MI. Prolongation of repolarization may be further augmented when local activation is earliest or electrogram voltage is decreased within scar.

Changed Duration of Ventricle Repolarization in Dog Heart under Conditions of Increased Preload

The duration of repolarization of subendocardial, intramural, and epicardial layers of dog ventricles was studied under conditions of volume overload of the heart in situ. Increased preload was modeled by rapid intravenous infusion of saline and rheopolygluquine. The activation-recovery interval was measured by flexible intramural electrodes inserted into the right and left ventricles. The level of preload was evaluated by the increase in left-ventricular end-diastolic pressure. The increase in preload from 11+/-6 to 26+/-10 mm Hg led to a significant (p<0.05) prolongation of the activation-recovery interval in the subepicardial layers of apex, all layers of the lateral wall, and subepicardial and intramural layers of the base of the left ventricle and in subendocardial layers of the apex and base of the right ventricle. Further elevation of the end-diastolic pressure to 34+/-11 mm Hg led to shortening of the activation-recovery interval (p<0.05) in the subepicardial layers of the apex and lateral wall of the left ventricle and in the subepicardial layers of right-ventricular base and left-ventricular lateral wall. Hence, different areas of the myocardium differently react to volume overload of the heart. Changes in repolarization length in response to preload increase are biphasic.

A reliability analysis of cardiac repolarization time markers

Only a limited number of studies have addressed the reliability of extracellular markers of cardiac repolarization time, such as the classical marker RT eg defined as the time of maximum upslope of the electrogram T wave. This work presents an extensive three-dimensional simulation study of cardiac repolarization time, extending the previous one-dimensional simulation study of a myocardial strand by Steinhaus [B.M. Steinhaus, Estimating cardiac transmembrane activation and recovery times from unipolar and bipolar extracellular electrograms: a simulation study, Circ. Res. 64 (3) (1989) 449]. The simulations are based on the bidomain – Luo-Rudy phase I system with rotational fiber anisotropy and homogeneous or heterogeneous transmural intrinsic membrane properties. The classical extracellular marker RT eg is compared with the gold standard of fastest repolarization time RT tap , defined as the time of minimum derivative during the downstroke of the transmembrane action potential (TAP). Additionally, a new extracellular marker RT 90 eg is compared with the gold standard of late repolarization time RT 90 tap , defined as the time when the TAP reaches 90% of its resting value. The results show a good global match between the extracellular and transmembrane repolarization markers, with small relative mean discrepancy ( ⩽ 1.6 % ) and high correlation coefficients ( ⩾ 0.92 ) , ensuring a reasonably good global match between the associated repolarization sequences. However, large local discrepancies of the extracellular versus transmembrane markers may ensue in regions where the curvature of the repolarization front changes abruptly (e.g. near front collisions) or is negligible (e.g. where repolarization proceeds almost uniformly across fiber). As a consequence, the spatial distribution of activation-recovery intervals (ARI) may provide an inaccurate estimate of (and weakly correlated with) the spatial distribution of action potential durations (APD).

There is no transmural heterogeneity in an index of action potential duration in the canine left ventricle

Transmural heterogeneity in ventricular repolarization demonstrated in vitro has been difficult to confirm in vivo. Whether this discrepancy reflects a physiological phenomenon or a methodological problem remains a vivid matter of debate despite a plethora of experimental work. Therefore, we have measured the relevant electrophysiological parameters first in vivo and repeated these in the same heart and at identical sites in vitro. Methodological issues were tackled by using both unipolar and bipolar recordings. Physiological issues were explored by measuring both local and functional electrophysiological parameters. In 10 healthy dogs, 2 high-resolution needle electrodes were inserted into the left ventricle. Effective refractory periods (ERP) as well as activation recovery intervals (ARI) were determined at each electrode along both needles at basic cycle lengths (BCL) of 850 and 300 ms, respectively. After excision of the heart, ERP and ARI measurements were repeated in the arterially perfused wedge preparations. First, we observed that ERPs and ARIs were significantly shorter in vivo than in vitro. Mean ERPs and ARIs of all muscle layers were relatively uniform throughout the ventricular wall in vivo. The transition from the in vivo to the in vitro preparation was associated with a significant albeit small increase of mean ARIs in the subendocardium, whereas interlayer differences in mean ERPs did not reach statistical significance as in vivo. In the intact canine left ventricular wall, a more or less homogeneous distribution in transmural ERP and ARI is present.

Estimating Atrial Action Potential Duration from Electrograms

Electrogram analysis is important in clinical and experimental settings. Activation recovery interval (ARI) has been used to measure ventricular action potential duration (APD) but its suitability for the atria has not been addressed. Mapping of atrial repolarization may be especially important during nerve stimulation since large heterogenous APD changes may manifest. This study assessed the utility of estimating APD in the atria using electrograms. A computer model of the atria was used to compute electrograms. Two different atrial waveforms were used, as well as two ventricular. APD was modulated with an acetylcholine- (ACh) dependent potassium channel and varying the spatial ACh distribution. ARI was computed, as well as the area under the repolarization wave (ATa). APD was measured by four methods. Atrial electrograms were also compared to monophasic action potentials recorded from a dog. ARI computed from atrial action potentials was not very precise, with errors ranging over 30 ms. Determining changes in APD induced by changing [ACh] yielded larger errors. Conversely, ventricular action potentials produced ARIs that very closely correlated with APD, and changes in APD . Positive ATa indicated regions of shortened APD, and islands of ACh release were clearly demarcated by ATa polarity. Experimentally, ARI was able to detect changes in APD, but did not measure APD well. The faster rate of ventricular repolarization produces larger currents that are less susceptible to electrotonic coupling effects, improving correlation with APD. ARI most closely correlated with APD measured as a fixed threshold above rest. Atrial APs produce electrograms that can be used to detect changes in APD. This may be improved by decreasing coupling. The ATa is a robust measure for precisely identifying spatial APD heterogeneities.

Interaction of Activation–Repolarization Coupling and Restitution Properties in Humans

Dynamic modulation of repolarization is important in arrhythmogenesis. An inverse relation exists in myocardium between activation time (AT) and action potential duration (APD). We hypothesized that resulting gradients of APD and diastolic interval (DI) interact with restitution properties and modulate the timing of repolarization. Activation-recovery intervals (ARI) were acquired from reconstructed noncontact unipolar electrograms from the left ventricular endocardium in 9 patients (7 male) with normal ventricles. At a basic paced cycle length (median, 450 ms), ARIs shortened along the path of activation, with a mandatory reciprocal increase of DIs. In the median patient, this range of DIs started at 230 ms at the site of earliest activation and increased to 279 ms at the site of latest activation at a basic cycle length of 450 ms. Four consecutive standard S1 to S2 restitution curves were performed. At sites with a longer ARI (and therefore shorter DI) close to the site of stimulation, premature stimulation produced more shortening of ARIs; therefore, the time course of restitution was steeper than at more distal sites. At normal heart rate, the decrease in ARIs along the conduction pathway compensated for later activation. Thus, dispersion in repolarization time (RT) is smaller than dispersion in ARI in a heart with a steep negative AT-ARI relationship. This protective effect is lost in hearts without such a relationship. In the patients with a steep AT-ARI relationship at basic cycle length, this relation is lost after premature stimulation and is a function of prematurity. Thus, dispersion in RT is larger after shortly coupled extra stimuli in patients with a steep AT-ARI relationship. A complex interplay exists between activation-repolarization coupling and restitution properties, largely driven by ARI and DI gradients. This plays a significant role in the dynamics of repolarization in humans.

Is there a significant transmural gradient in repolarization time in the intact heart?

Is there a significant transmural gradient in repolarization time in the intact heart?

The effect of enhanced gap junctional conductance on ventricular conduction in explanted hearts from patients with heart failure

To investigate ventricular conduction and refractoriness before and after application of rotigaptide, an enhancer of gap junctional conductance, to explanted hearts of patients with heart failure (HF). In six explanted perfused hearts of patients with end-stage HF, activation/repolarization mapping was performed and refractory periods (RPs) and activation recovery intervals (ARIs) were measured before and after application of 50 nM rotigaptide. Rotigaptide caused a decrease of RP from 476 +/- 36 to 453 +/- 31 ms (P < 0.05), but did not change ARI-dispersion. During premature activation along the fibers rotigaptide decreased the minimal activation time (AT(min)) and maximal activation time (AT(max)) significantly from 35 +/- 12 to 24 +/- 9 and from 97 +/- 38 to 43 +/- 7 ms, respectively. Rotigaptide did not change AT(min) and AT(max) during activation perpendicular to the fiber direction. After application of rotigaptide conduction curves normalized in five/six recordings when activation was parallel, but destabilized in three/six hearts when activation was perpendicular to fiber direction. The destabilization was associated with local conduction delays rather than with facilitation of conduction. Rotigaptide applied to hearts of patients with end-stage HF shortened RPs normalized conduction curves and increased conduction parallel to fiber direction. However, in 50% of the hearts local slowing of conduction with destabilization of conduction (curves) occurs at sites close to the stimulation site, when activation is perpendicular to fiber direction.

Effects of ectopic pacing on repolarization of the chicken left ventricle

Effects of ectopic pacing on left ventricular repolarization were studied in six anesthetized open-chest chickens. In each animal, unipolar electrograms were acquired from as many as 98 sites with 14 plunge needles (seven transmural locations between epicardium and endocardium in each needle). Activation-recovery intervals (ARIs), corrected to the cycle length, were used for estimating repolarization. At baseline, the nonuniform ARI distribution in the left ventricle resulted in the apicobasal differences being greater than the transmural gradient. Nonuniform ARI prolongation caused by ectopic pacing resulted in decreasing the transmural repolarization gradient and increasing the differences in the apex-to-base direction. The basal, but not apical transmural differences contributed to the total left ventricular transmural gradient. The total left ventricular apicobasal gradient was contributed by the apicobasal differences in mid-myocardial and subendocardial layers more than in subepicardial ones. Thus, in in situ chicken hearts, the transmural and apicobasal ARI gradients exist within the left ventricle with the shortest ARIs in the basal subepicardium and the longest ARIs in the subendocardium of the apical and middle parts of the left ventricle. Apicobasal compared to transmural heterogeneity of local repolarization properties contributes more to the total left ventricular repolarization gradient.

Effects of Procainamide and Sotalol on Restitution Properties, Dispersion of Refractoriness, and Ventricular Fibrillation Activation Patterns in Pigs

Interest in combining antiarrhythmic drugs has been prompted by the lack of efficacy of monotherapies and the toxicity resulting from high doses of individual agents. We tested the hypothesis that procainamide and sotalol combined have greater beneficial effects on restitution, on the dispersion of refractoriness, and on decreasing the complexity of ventricular fibrillation (VF) than either drug alone. Six open-chest pigs received intravenous procainamide (15 mg/kg load and 50 microg/kg/min maintenance) followed by sotalol (1.5 mg/kg). Another six pigs received sotalol first and procainamide second. Before drugs and after each drug, 20-second episodes of electrically induced VF were recorded from a 21 x 24 unipolar electrode plaque (2 mm spacing) sutured on the lateral posterior left ventricular epicardium. Restitution properties and dispersion of refractoriness were estimated from activation recovery intervals during pacing. The combination of the two drugs reduced the maximum slope of the restitution curve and during VF reduced the number of wavefronts, the activation rate, the percentage of wavefront families exhibiting reentry, and the conduction velocity more than either drug alone. In addition, in the group that received sotalol first, both drugs together reduced the SD and the coefficient of variation of the spatial dispersion of refractoriness compared with baseline. Procainamide and sotalol combined have greater beneficial effects on restitution properties, dispersion of refractoriness, and the complexity of VF than either drug alone compared with baseline.

Intracoronary Infusion of Catecholamines Causes Focal Arrhythmias in Pigs

Acute ischemia causes myriad changes including increased catecholamines. We tested the hypothesis that elevated catecholamines alone are arrhythmogenic. A 504 electrode sock was placed over both ventricles in six open-chest pigs. During control infusion of saline through a catheter in the left anterior descending coronary artery (LAD), no sustained arrhythmias occurred, and the refractory period estimated by the activation recovery interval (ARI) was 175 +/- 14 ms in the LAD bed below the catheter. After infusion of isoproterenol at 0.1 microg/kg/min through the catheter, the ARI in this bed was significantly reduced to 109 +/- 10 ms. A sharp gradient of refractoriness of 43 +/- 10 ms was at the border of the perfused bed. Sustained monomorphic ventricular tachycardia occurred after drug infusion in the perfused bed or near its boundary in all animals with a cycle length of 329 +/- 26 ms and a focal origin. The maximum slope of the ARI restitution curve at the focal origins of the tachyarrhythmias was always <1 (0.62 +/- 0.15). Similar results with a focal arrhythmia origin occurred in two additional pigs in which intramural mapping was performed with 36 plunge needle electrodes in the left ventricular perfused bed. Regional elevation of a catecholamine, which is one of the alterations produced by acute ischemia, can by itself cause tachyarrhythmias. These arrhythmias are closely associated with a shortened refractory period and a large gradient of the spatial distribution of refractoriness but not with a steep restitution curve.

Cardiac Memory in Patients With Wolff-Parkinson-White Syndrome

Background— Cardiac memory refers to a change in ventricular repolarization induced by and persisting for minutes to months after cessation of a period of altered ventricular activation (eg, resulting from pacing or preexcitation in patients with Wolff-Parkinson-White syndrome). ECG imaging (ECGI) is a novel imaging modality for noninvasive electroanatomic mapping of epicardial activation and repolarization. Methods and Results— Fourteen pediatric patients with Wolff-Parkinson-White syndrome and no other congenital disease, were imaged with ECGI a day before and 45 minutes, 1 week, and 1 month after successful catheter ablation. ECGI determined that preexcitation sites were consistent with sites of successful ablation in all cases to within a 1-hour arc of each atrioventricular annulus. In the preexcited rhythm, activation-recovery interval (ARI) was the longest (349±6 ms) in the area of preexcitation leading to high average base-to-apex ARI dispersion of 95±9 ms (normal is ≈40 ms). The ARI dispersion remained the same 45 minutes after ablation, although the activation sequence was restored to normal. ARI dispersion was still high (79±9 ms) 1 week later and returned to normal (45±6 ms) 1 month after ablation. Conclusions— The study demonstrates that ECGI can noninvasively localize ventricular insertion sites of accessory pathways to guide ablation and evaluate its outcome in pediatric patients with Wolff-Parkinson-White syndrome. Wolff-Parkinson-White is associated with high ARI dispersion in the preexcited rhythm that persists after ablation and gradually returns to normal over a period of 1 month, demonstrating the presence of cardiac memory. The 1-month time course is consistent with transcriptional reprogramming and remodeling of ion channels.

Clinical Summaries

Clinical Summaries

Olea europaea leaf extract exerts L-type Ca 2+ channel antagonistic effects

Ethnopharmacological relevance In Southern Europe Olea europaea leafs are known as a folk remedy for hypertension. Cardiovascular diseases are still the leading causes of morbidity and mortality in industrialized countries with hypertension being one of the main risk factors. Aim of the study We investigated effects of a commercial Olea europaea leaf extract (OLE) on isolated hearts and cultured cardiomyocytes. Materials and methods Isolated rabbit hearts were perfused according to the Langendorff technique and connected to a 256-channel epicardial mapping system. Voltage clamp experiments were performed in cultured neonatal rat cardiomyocytes using a perforated-patch technique. Results OLE caused a concentration-depended decrease in systolic left ventricular pressure and heart rate as well as an increase in relative coronary flow and a slight, but not significant prolongation of PQ-time. There were no significant changes between the groups in the activation-recovery interval and its dispersion, total activation time, peak-to-peak amplitude, percentage of identical breakthrough-points and similar vectors of local activation. Voltage clamp experiments in cultured neonatal rat cardiomyocytes showed a significant decrease in maximum I Ca,L by OLE which was reversible upon wash-out. Conclusions OLE suppresses the L-type calcium channel directly and reversibly. Our findings might help to understand the traditional use of OLE in the treatment of cardiovascular disease.