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Biomedical subjects

N el-Sherif

Publications and source records attributed to N el-Sherif.

At least 55 records · Page 3Linked to original sources
PubMed1992

Adrenergic effects on reentrant ventricular rhythms in subacute myocardial infarction.

BACKGROUND: Reentry has been shown to be a mechanism of ventricular arrhythmias elicited by programmed premature stimulation in the subacute ischemic period of dogs subjected to myocardial infarction. The spatial distribution of refractoriness in these hearts has been shown to play an important part in the formation of functional arcs of conduction block during programmed ventricular stimulation. Because the adrenergic nervous system influences cardiac arrhythmias and myocardial infarction can directly affect sympathetic innervation in the heart, we investigated the role of the sympathetic nervous system on reentry in the canine heart 4 days after infarction. METHODS AND RESULTS: The influences of adrenergic stimuli on the initiation of reentrant ventricular excitation were studied using a 128-channel computerized recording system in the canine heart 4 days after ligation of the left anterior descending coronary artery. Bilateral stimulation of the ansae subclavia preferentially improved conduction of premature beats in the normal zones. This corresponded to an improvement in excitability, as measured by a decrease in stimulus strength at the same premature coupling interval as control. Consequently, the effective refractory period was preferentially shortened at normal sites but not at ischemic sites. Both of these changes contributed to a shift of the arc of functional conduction block toward more normal tissue. As a result, sites proximal to the arc of functional conduction block had more time to recover excitability and thereby were available to be reexcited by the distal activation wave front. Conversely, intravenous infusion of norepinephrine preferentially shortened the effective refractory period of sites in the ischemic zone, thereby indicating that denervation hypersensitivity had occurred at these sites. The spatial dispersion of refractoriness and the arc of functional conduction block were significantly reduced in size. As a consequence, previously inducible reentrant rhythms were no longer inducible. CONCLUSIONS: Sympathetic stimulation can be considered an arrhythmogenic intervention, whereas norepinephrine infusion may be considered antiarrhythmic in this experimental model.

Animals↗
PubMed1992

Dose-dependent modulation of the cardiac sodium channel by sea anemone toxin ATXII.

The effects of sea anemone toxin ATXII on single sodium channels were studied in cell-attached patches on rabbit ventricular myocytes at 20-22 degrees C. Exposure of patches to 1,000 nM ATXII induced long-lasting bursts of openings, which were more dramatically different from control at -20 mV than at -50 mV. Mean open duration, which had a biphasic dependence on voltage in control patches, was monotonically dependent on voltage in toxin-exposed patches, being 3.5 times longer than control at -20 mV and 4.5 times longer at -10 mV. Multiple mean open durations were detected at depolarized potentials. To test whether the multiple mean open durations resulted from a mixture of modified and unmodified openings, histograms of late openings (when unmodified channels would be inactivated) were constructed. Because in most cases these fit a single exponential with a mean open duration like that of modified channels, we conclude that voltage-dependent toxin unbinding produced a mixed population of unmodified and modified openings. Consistent with this hypothesis, lower concentrations of toxin most often produced open-duration histograms best fit with two exponentials. Ensembles revealed complex decay kinetics, which could be interpreted within the context of the toxin-induced increase in mean open duration and burst duration and the summation of modified and unmodified events. Analysis of the numbers of early versus late events at -20 mV for patches exposed to 20 nM, 100 nM, and 1,000 nM ATXII predicted the ED50 for ATXII block to be 285 nM at this potential. Using a five-state Markovian model, the action of ATXII could be explained as a reduction of the open-to-inactivated rate constant without effect on inactivation from closed states or other rate transitions.

Animals↗
PubMed1991

Events in the cardiac arrhythmia suppression trial: baseline predictors of mortality in placebo-treated patients.

Patients randomized to placebo in the encainide and flecainide arms of the Cardiac Arrhythmia Suppression Trial (CAST) have been found to have a relatively low 1-year mortality rate of 3.9% in comparison with previous studies of patients in the postmyocardial infarction period. To determine the comparability of CAST with previous studies, baseline variables were examined in the 743 patients randomized to placebo in the flecainide and encainide arms of CAST. Twenty-three baseline characteristics were correlated with major outcome events: arrhythmic death (16 events), total mortality (26 events) and congestive heart failure (51 events). On multivariate analysis the risk of new or worsening congestive heart failure was significantly associated with diuretic use, diabetes, high New York Heart Association functional class, age, prolonged QRS duration and low ejection fraction. The risk of arrhythmic death or resuscitated cardiac arrest was significantly associated with an index Q wave myocardial infarction, history of heart failure, use of digitalis, diabetes and prolonged QRS duration. Total mortality or resuscitated cardiac arrest was significantly associated with an index Q wave myocardial infarction, diabetes, ST segment depression, high functional class, prolonged QRS duration and low ejection fraction. The variables at baseline associated with mortality from all causes or arrhythmic death or resuscitated cardiac arrest and heart failure in the CAST placebo-treated patients are similar to those identified in previous postmyocardial infarction studies. Thus, the observation of increased mortality in CAST associated with the administration of encainide and flecainide for suppression of ventricular premature depolarizations is probably applicable to any comparably defined group of patients in the postmyocardial infarction period.

Aged↗
PubMed1991

Spectral turbulence analysis of the signal-averaged electrocardiogram and its predictive accuracy for inducible sustained monomorphic ventricular tachycardia.

This study was designed to assess the accuracy of a new noninvasive frequency analysis method for predicting patients with inducible sustained monomorphic ventricular tachycardia (VT) at electrophysiologic study and hence the risk of spontaneous ventricular tachyarrhythmias. Signal-averaged electrocardiograms from 3 orthogonal bipolar surface leads were evaluated using a microcomputer-based frequency analysis system that performs analysis of conventional time-domain late potentials as well as incorporating a new technique for spectral analysis of relatively short, overlapping signal segments spanning the whole QRS complex. The spectral analysis technique measured abnormalities anywhere in the entire QRS complex and did so without dependence on any arbitrarily defined frequency, duration or amplitude cutoffs. The hallmark of arrhythmogenic abnormality was hypothesized to be frequent and abrupt changes in the frequency signature of the QRS wave front velocity as it propagates throughout the ventricle around areas of abnormal conduction, resulting in a high degree of spectral turbulence. One-hundred forty-two subjects were studied, including 71 totally normal control subjects ("true negatives"), 33 with both late potentials by time-domain analysis and inducible sustained monomorphic VT ("true positives"), 28 with late potentials but no evidence of spontaneous or inducible sustained monomorphic VT ("false positives") and 10 with inducible sustained monomorphic VT but absence of time-domain late potentials ("false negatives"). The frequency analysis technique correctly classified 100% of the true negatives, 97% of the true positives, 86% of the late potentials false positives and 60% of the late potentials false negatives. The total predictive accuracy of frequency analysis for all groups was 94%, compared with 73% for time-domain late potential analysis. The results suggest that a high degree of spectral turbulence of the overall QRS signal during sinus rhythm may provide a more accurate marker for the anatomic-electrophysiologic substrate of reentrant tachyarrhythmias than detection of late potentials in the terminal QRS region by either time- or frequency-domain analysis. Spectral turbulence analysis is applicable to patients irrespective of the QRS duration and the presence or absence of bundle branch block.

Electrocardiography↗
PubMed1991

Spontaneous myocardial ischemia and the signal-averaged electrocardiogram.

The effects of transient myocardial ischemia on the signal-averaged electrocardiogram were investigated in 13 patients with coronary artery disease and spontaneous angina undergoing 3-channel ambulatory electrocardiography. Ischemia was seen as ST elevation in 2 patients or ST depression in 11; it was anterior in 5 patients, inferior in 4 and undefined in 4. Signal-averaged electrocardiograms with noise levels less than or equal to 1 microV were obtained from Holter tapes during 54 of 61 ischemic attacks recorded in the study group (88%), and compared with 54 tracings recorded within 60 minutes of the index attacks. Baseline tracings were normal in 8 patients (62%), showed a long QRS duration in 2 (15%), and both a long QRS duration and a late potential in the remaining 3 (23%). Comparison of recordings at baseline and during ischemic attacks revealed no significant changes in signal-averaged electrocardiographic parameters. Absence of significant differences was also noted when analysis was performed according to the type of ischemic attacks (associated with ST elevation [n = 14] or ST depression [n = 40]), their location (anterior [n = 21] or inferior [n = 23]), their duration (greater than 10 minutes [n = 29] or less than or equal to 10 minutes [n = 25]), and their magnitude (greater than 2 mm [n = 18] or less than or equal to 2 mm [n = 36]). It is concluded that spontaneous transient myocardial ischemia, independent of its type, location, duration and magnitude, does not generate a substrate for late potentials on the signal-averaged electrocardiogram.

Aged↗
PubMed1991

Electrophysiologic mechanisms of ventricular arrhythmias.

In this work the electrophysiologic mechanisms of ventricular arrhythmias have been briefly summarized. Ventricular arrhythmias can be caused either by pacemaker activity or by reentrant excitation. Enhancement of normal automaticity can generate a parasystolic rhythm in normal fibers. Abnormal automaticity may arise from fibers in which maximum diastolic potential has been reduced by a variety of interventions. Triggered activity is caused by either an early (EAD) or delayed (DAD) afterdepolarization and requires a prior normal action potential for initiation. While there is growing evidence that EAD-induced triggered activity plays a significant role in the Long QTU syndrome and Torsade de Pointes, no clinical arrhythmias has definitely been ascribed to DADs, although DADs have been recorded in man after acute digoxin intoxication. Ventricular arrhythmias can be also caused by reentrant excitation, which can be subdivided into reflection or circus movement reentry (CMR). In the reflection model impulses in both directions are transmitted over the same pathway. In the CMR three models can be differentiated: the ring model, which requires a fixed anatomical obstacle; the figure-eight model and the leading circle model, where functional rather than fixed anatomical obstacles are involved.

Action Potentials↗
PubMed1991

Study of the influence of left bundle branch block on the signal-averaged electrocardiogram: a qualitative and quantitative analysis.

UNLABELLED: To study the influence of left bundle branch block (LBBB) on the signal-averaged electrocardiogram (SAECG), quantitative and qualitative analyses of SAECG parameters were undertaken in 48 patients with electrocardiographic evidence of intrinsic LBBB and in 39 patients with a "normal" surface QRS duration (less than 120 msec) who underwent right ventricular pacing-induced LBBB. We assumed pacing of the right ventricular apex to be a suitable model of this conduction defect. Sustained monomorphic ventricular tachycardia (SMVT) was inducible in 16 of 48 patients with intrinsic LBBB and in 23 of 39 patients with pacing-induced LBBB. Utilizing a filter setting of 25 to 250 Hz, late potentials were defined as a total filtered QRS duration greater than or equal to 120 msec, a root mean square voltage in the terminal 40 msec (RMS 40) of less than or equal to 25 microV, and the duration of signals less than 40 microV (LAS 40) of greater than or equal to 38 msec. Only RMS 40 and LAS 40 criteria were used in patients with LBBB. Prolongation of LAS 40 and fragmentation of signals in the terminal portion of the filtered QRS were characteristic of all patients with LBBB aberration. Of those patients with intrinsic LBBB, the mean total filtered QRS duration, RMS 40, and LAS 40 for inducible and noninducible patients were significantly different (170 +/- 28, 16 +/- 10, 55 +/- 24, and 153 +/- 18 msec, 25 +/- 10 microV, 33 +/- 16.9 msec; p = 0.04, 0.009, and 0.007, respectively). Noninducible patients with a normal QRS duration demonstrated a 60% decrement in the mean RMS 40 value during pacing-induced LBBB. These changes resulted in a 59% false positive incidence of late potentials during pacing-induced LBBB. This correlated with a similarly low mean RMS 40 value in patients with intrinsic LBBB and no inducible SMVT, hence giving rise to a false positive incidence of late potentials of 63%. Since "standard" RMS 40 and LAS 40 criteria resulted in low specificity and positive predictive value, new parameters were selected and analyzed. The combination of RMS 40 less than or equal to 17 microV plus LAS 40 greater than or equal to 55 msec yielded the best overall statistical result, with a sensitivity, specificity, and total predictive accuracy of 69%, 81%, and 77%, respectively. IN CONCLUSION: (1) A reduction of RMS 40, prolongation of LAS 40, and fragmentation of signals in the terminal portion of the filtered QRS are characteristics of LBBB.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1991

Alpha 1-adrenoceptor regulation of delayed afterdepolarizations and triggered activity in subendocardial Purkinje fibers surviving 1 day of myocardial infarction.

Alpha 1-adrenoceptor agonists were shown to induce delayed afterdepolarizations (DADs) and triggered activity in the presence of elevated extracellular Ca2+. We investigated the effects of alpha 1-adrenoceptor stimulation on DADs and triggered activity in canine Purkinje fibers that survived 1-day of myocardial infarction. Endocardial preparations were studied using standard microelectrode techniques. In quiescent preparations showing no DADs and in presence of propranolol (2 x 10(-7) M), phenylephrine (10(-6) M), an alpha 1-adrenoceptor agonist induced DADs (n = 6) and differentially induced triggered activity in ischemic but not in normal Purkinje fibers (n = 4). In 8 preparations that showed subthreshold DADs, phenylephrine increased the DAD amplitude from 4.0 +/- 2.5 mV to 8.0 +/- 3.3 mV (P less than 0.03) and from 3.2 +/- 1.5 mV to 6.5 +/- 3.7 mV (P less than 0.05) at paced cycle lengths of 800 and 400 ms, respectively. Phenylephrine caused subthreshold DADs to reach threshold and result in triggered activity (n = 6). The effects of phenylephrine were abolished by 10(-6) M prazosin, an alpha 1-adrenoceptor blocker. Our results suggest that alpha 1-adrenoceptor stimulation regulates DADs and triggered activity seen in subendocardial Purkinje fibers surviving 1 day of myocardial infarction and may contribute to the spontaneous ventricular tachycardia seen in vivo at this stage.

Action Potentials↗
PubMed1991

Standards for analysis of ventricular late potentials using high-resolution or signal-averaged electrocardiography: a statement by a task force committee of the European Society of Cardiology, the American Heart Association, and the American College of Cardiology.

Sufficient data are available to recommend the use of the high-resolution or signal-averaged electrocardiogram in patients recovering from myocardial infarction without bundle branch block to help determine their risk for developing sustained ventricular tachyarrhythmias. However, no data are available about the extent to which pharmacological or nonpharmacological interventions in patients with late potentials have an impact on the incidence of sudden cardiac death. Therefore, controlled, prospective studies are required before this issue can be resolved. As refinements in techniques evolve, it is anticipated that the clinical value of high-resolution or signal-averaged electrocardiography will continue to increase.

Analog-Digital Conversion↗
PubMed1991

Pharmacological evaluation of early afterdepolarisations induced by sea anemone toxin (ATXII) in dog heart.

STUDY OBJECTIVE: ATXII is a polypeptide toxin isolated from the sea anemone, Anemonia sulcata, known to delay sodium inactivation markedly and to induce early afterdepolarisations. The aim was to investigate the mechanism of its action. DESIGN AND MATERIALS: The mechanism of ATXII induced early afterdepolarisations was investigated in vitro in canine endocardial preparations using standard microelectrode techniques. MEASUREMENTS AND MAIN RESULTS: ATXII (2 x 10(-7) M) induced cycle length dependent prolongation of plateau, more marked in Purkinje than in muscle fibres, and early afterdepolarisations in Purkinje fibres only. The calcium channel antagonists verapamil (10(-6) M, 10(-5) M) and cobalt (2-4 mM), and drugs that block calcium release from the sarcoplasmic reticulum, ryanodine (10(-6) M, 10(-5) M) and caffeine (10 mM), did not antagonise the ATXII effects. However, tetrodotoxin (5 x 10(-6) M) and lignocaine (4 x 10(-5) M) shortened the action potential and suppressed early afterdepolarisations. The effects of lignocaine were seen at concentrations that did not significantly affect Vmax. CONCLUSIONS: ATXII induced early after depolarisations are due to the effects of ATXII on Na+ entry, probably via a slowly inactivated Na+ channel population. Calcium entry through the sarcolemmal Ca2+ channels and cyclic Ca2+ release from the sarcoplasmic reticulum are not required for the genesis of early afterdepolarisations in this model.

Animals↗
PubMed1991

Standards for analysis of ventricular late potentials using high resolution or signal-averaged electrocardiography. A statement by a Task Force Committee between the European Society of Cardiology, the American Heart Association and the American College of Cardiology.

Sufficient data are available to recommend that the high-resolution or signal-averaged electrocardiogram can be used in patients recovering from myocardial infarction without bundle branch block to help to determine their risk for developing sustained ventricular tachyarrhythmias. However, no data are available regarding the extent to which pharmacologic or non-pharmacologic interventions in patients with late potentials have an impact on the incidence of sudden cardiac death. Therefore, controlled, prospective studies are required before this issue can be definitely answered. As refinements in techniques evolve, it is anticipated that the clinical value of high-resolution or signal-averaged electrocardiography will continue to increase in the future.

Arrhythmias, Cardiac↗
PubMed1991

Reentrant ventricular arrhythmias in the late myocardial infarction period: mechanism by which a short-long-short cardiac sequence facilitates the induction of reentry.

The electrophysiological mechanism by which a short-long-short stimulated cardiac sequence facilitates the induction of ventricular tachyarrhythmia was investigated in dogs 4 days after ligation of the left anterior descending coronary artery. In these dogs, reentry develops in the surviving electrophysiologically abnormal epicardial layer that overlies the infarct zone when premature stimulation results in a critically long arc of functional conduction block. The activation wavefront circulates around both ends of the arc, coalesces, and conducts slowly distal to the arc before reactivating sites proximal to the arc to initiate a figure-eight reentrant circuit. Epicardial isochronal activation maps and effective refractory periods (ERPs) were determined during three different stimulation protocols: A, a basic train of eight beats at a cycle length of 300 msec followed by a single premature stimulus (S2); B, a basic train of eight beats at a cycle length of 300 msec with abrupt lengthening of the last cycle of the train before S2 to 600 msec; C, a basic train of eight beats at a cycle length of 600 msec followed by S2. Protocol B was found to result in a differential lengthening of ERP at adjacent sites within the border of the epicardial ischemic zone, whereas protocols A and C induced, respectively, comparable shortening and lengthening of ERPs at the same sites. The differential lengthening of ERPs at adjacent sites resulted in an increased dispersion of refractoriness so that a premature stimulus induced functional conduction block between those sites. The development of a longer arc of conduction block and, hence, a longer reentrant pathway as well as slower conduction of the circulating wavefront during protocol B allowed more time for refractoriness to expire proximal to the arc and for the circulating wavefront to reexcite those sites to initiate reentry. The lengthening of ERP, associated with a single long cycle (protocol B), ranged from 44% to 79% of the total increase in ERP after a series of eight long cycles (protocol C). Epicardial sites with longer ERPs located close to the center of the ischemic zone showed more lengthening of refractoriness during protocol B compared with more normal sites near the border of the ischemic zone. This strongly suggests that the increased dispersion of refractoriness during protocol B is caused by the shorter memory of ischemic myocardium to the cumulative effects of preceding cycle lengths.

Animals↗
PubMed1991

Standards for analysis of ventricular late potentials using high-resolution or signal-averaged electrocardiography. A statement by a Task Force Committee of the European Society of Cardiology, the American Heart Association, and the American College of Cardiology.

Sufficient data are available to recommend the use of the high-resolution or signal-averaged electrocardiogram in patients recovering from myocardial infarction without bundle branch block to help determine their risk for developing sustained ventricular tachyarrhythmias. However, no data are available about the extent to which pharmacological or nonpharmacological interventions in patients with late potentials have an impact on the incidence of sudden cardiac death. Therefore, controlled, prospective studies are required before this issue can be resolved. As refinements in techniques evolve, it is anticipated that the clinical value of high-resolution or signal-averaged electrocardiography will continue to increase.

American Heart Association↗
PubMed1991

Circus movement atrial flutter in canine sterile pericarditis model. Activation patterns during entrainment and termination of single-loop reentry in vivo.

BACKGROUND: Recently, we used a custom designed "jacket" electrode with 127 bipolar electrodes in a flexible nylon matrix to map the total atrial epicardial surface in the in situ canine heart. Atrial flutter in dogs with sterile pericarditis was shown to be due to a single wave front circulating around a combined functional/anatomic obstacle, with the arc of functional conduction block contiguous with one or more of the atrial vessels. METHODS AND RESULTS: In the present study, this model was used to analyze the activation pattern during pacing-induced entrainment and termination of single reentrant loops in a syncytium without anatomically predetermined pathways. Sustained atrial flutter was induced in five dogs with 3-5-day-old sterile pericarditis. Atrial pacing at a cycle length 5-30 msec shorter than the spontaneous cycle length entrained the arrhythmia and could result in a "classical" activation pattern, characterized by an antidromic stimulated wave that collided with the reentrant orthodromic wave front of the previous beat at a constant site. However, two variations of this classical activation pattern were also observed: 1) Pacing at short cycle lengths could lead to localized conduction block in antidromic direction, forcing a change in the pathway of the antidromic wave front. This could prevent the expected shift of the site of collision in antidromic direction. 2) The stimulated orthodromic wave front could also use a pathway different from that of the original reentrant impulse, so that a different circuit was active during the pacing period. Termination of atrial flutter by rapid atrial stimulation was associated with progressive slowing and finally blocking of the paced orthodromic wave front and a progressive shift of the site of collision in antidromic direction. The occurrence of conduction block was determined by the cycle length of stimulation and the number of stimulated beats. A longer train at the critical cycle length or the critical number of beats at a shorter cycle length could reinduce the same reentrant circuit or a different reentrant circuit, respectively, during stimulated cycles following the beat that terminated reentry. CONCLUSIONS: The epicardial activation sequence during entrainment of reentrant arrhythmias does not necessarily follow a standard activation pattern. Instead, the stimulated orthodromic as well as the antidromic wave front might use a pathway different from that of the original reentrant wave front. The mechanisms of termination, failure of termination, and reinitiation of single-loop reentry are similar to those in the "figure-eight" reentrant circuit.

Animals↗
PubMed1991

Circus movement atrial flutter in the canine sterile pericarditis model. Differential effects of procainamide on the components of the reentrant pathway.

To evaluate the mechanisms of action of procainamide on the components of the reentrant pathway, drug-induced changes in activation patterns, effective refractory periods (ERPs), and stimulation thresholds were analyzed in nine dogs with sterile pericarditis and sustained atrial flutter. Activation maps were based on 127 close bipolar recordings from a special "jacket" electrode. From the control map, 22 +/- 2 sites covering the slow zone and the normal zone of the reentrant circuit were selected to measure ERPs and thresholds. The excitable gap was estimated from the longest ERP during pacing at the tachycardia cycle length. During atrial flutter, epicardial activation proceeded as a single wave around an arc of functional conduction block in the proximity of the atrioventricular (AV) ring or around a combined functional/anatomic obstacle, with the arc being contiguous with one of the venae cavae. An area of slow conduction, which accounted for 53 +/- 15% of the revolution time within 35 +/- 15% of the total length of the reentrant pathway, was bordered by the arc of block and the AV ring or a caval vein and the AV ring, respectively. Procainamide (5-10 mg/kg i.v.) prolonged the cycle length of atrial flutter from 144 +/- 17 to 190 +/- 24 msec (p less than 0.05) and then terminated the arrhythmia in all studies. The increase in cycle length was due to an increase in conduction time in the slow zone by 37 +/- 11 msec (86 +/- 17% of the total cycle length increase). During the last reentrant beat, conduction failed in the slow zone, with the arc of block joining the AV ring. At termination, procainamide had prolonged conduction time, stimulation threshold, and ERP in the normal zone by 11 +/- 18%, 40 +/- 80%, and 5 +/- 15%, respectively, compared with 51 +/- 16%, 86 +/- 93%, and 14 +/- 21%, respectively, in the slow zone (p less than 0.05 for all three parameters). The duration of the excitable gap did not change significantly. We conclude that procainamide preferentially affected the slow zone of single loop reentrant circuits. The drug terminated circus movement atrial flutter without abolishing the excitable gap, and its effect on conduction seemed the major determinant of the antiarrhythmic action.

Animals↗
PubMed1991

Early afterdepolarizations and arrhythmogenesis. Experimental and clinical aspects.

There is growing evidence that early afterdepolarizations (EADs) and EAD-induced triggered activity play a significant role in the clinical syndrome of long QTU and polymorphic ventricular tachyarrhythmias better known as Torsade de Pointes (TdP). This evidence is briefly examined in this report. The three steps required for the manifestation of EAD-induced triggered activity are: 1) critical prolongation of the repolarization phase, 2) a net depolarizing current carrying the charge for EAD, and 3) propagation of EADs which are locally generated to capture the entire heart resulting in one or more extrasystoles. The majority of pharmaceutical interventions associated with EADs could be grouped as acting predominantly through one of three different mechanisms 1) a delay of one or both potassium currents IK and Ikl, 2) an increase of transsarcolemmal calcium current (ICa), and 3) a delay of sodium current (INa) inactivation. Two experimental models in the dog utilized cesium and anthopleurin-A to produce bradycardia-dependent long QTU and polymorphic ventricular tachyarrhythmias that may resemble the clinical syndrome of long QTU and TdP. In both in vivo models, monophasic action potential (MAP) recordings demonstrated EADs-like deflections more prominent in endocardial than in epicardial recordings. The clinical syndrome of long QTU and TdP can be either congenital, idiopathic or acquired. Several observations suggest a common underlying mechanism with a greater predominance of adrenergic influence in the congenital or idiopathic long QTU syndrome. Adrenergic influence can act by enhancing the depolarizing current of EAD as well as EAD transmission in the intact heart.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗