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Biomedical subjects

N el-Sherif

Publications and source records attributed to N el-Sherif.

At least 91 records · Page 5Linked to original sources

Quinidine-induced long QTU interval and torsade de pointes: role of bradycardia-dependent early afterdepolarizations.

Right ventricular endocardial monophasic action potential recordings were obtained in a patient with a qunidine-induced long QTU interval and polymorphic ventricular tachycardia of the torsade de pointes type. The recording showed a deflection on phase 3 repolarization characteristic of early afterdepolarization. The early afterdepolarization was synchronous with the U wave in surface electrocardiographic leads and there was a strong correlation between the amplitude of both waves. A strong correlation was also present between the cardiac cycle length and the U wave amplitude with larger amplitudes after longer cycles. Ventricular ectopic beats occurred only after long cycle lengths and seemed to arise close to the peak of the U wave and early afterdepolarization. However, there was no correlation between the amplitude of the U wave or early afterdepolarization and the occurrence of ectopic beats. Rapid ventricular pacing resulted in suppression of the ectopic rhythm associated with suppression of both the U wave and the early afterdepolarization. This case provides the first evidence to suggest that a quinidine-induced long QTU interval and torsade de pointes may be related to bradycardia-dependent early afterdepolarizations, although other factors may be involved in triggering the arrhythmia.

Action Potentials↗

The signal-averaged electrocardiogram and late potentials. A comparative analysis of commercial devices.

The authors used two separate protocols to compare four commercially available devices for recording of the signal-averaged electrocardiogram and "late potentials" to assess their degree of concordance in identifying abnormalities. In one protocol, studies were performed using each system. In 19% of recordings the results from one system were discordant in at least one numeric parameter. In the second protocol identical averaged data files were used to identify discordancies due solely to differences in analysis algorithms used for QRS offset determination by the various devices. This disclosed 23% discordant findings, mostly in the root mean square amplitude of the terminal 40-msec segment resulting from small differences in the estimate of QRS offset point. To improve concordance between commercial systems, there is an urgent need for adoption of a rigorously standardized algorithm for analysis of baseline noise and QRS offset.

Action Potentials↗

Cryothermal mapping of the sinus node in dogs: a simple method of localising dominant and latent pacemakers.

To investigate the potential use of cryothermal mapping to localise the sites of the dominant and latent pacemakers of the sinus node, we compared the results of cryothermal and electrical mapping of the sinus node in 16 dogs. In all dogs, cooling (-5 to +5 degrees C) of a localised epicardial area of about 3 X 3 mm2 close to the sulcus terminalis (area 1) resulted in a decrease in heart rate and a change in the P wave configuration. Cooling of an additional area of up to 15 X 3 mm2 (area 2) while cooling of area 1 was maintained resulted in a further decrease in heart rate and a further change in P wave configuration until junctional rhythm occurred. In all dogs areas 1 and 2 could be identified within 5 min. The heart rate and P wave configuration returned to control following cooling suggesting no adverse effect of cooling on the sinus node in this temperature range. In dogs with sufficiently slow heart rates, recording from area 1 showed diastolic and upstroke slopes followed by primary negativity, indicating that area 1 was the area of the dominant pacemaker. Recording from area 2 showed only diastolic slopes indicating that area 2 was the area of the latent pacemaker. Compared to electrical mapping for identifying diastolic slope, upstroke slope and primary negativity or earliest atrial activation, cryothermal mapping is a simple, quick and safe procedure for localisation of the sinus pacemakers. Unlike recording of sinus nodal electrograms, cryothermal mapping can be performed in the presence of rapid heart rates.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The differential response of normal and ischaemic Purkinje fibres to clofilium, d-sotalol and bretylium.

To determine whether ischaemic tissue is more sensitive than normal tissue to class III anti-arrhythmic agents, we studied the effects of the class III agents clofilium, d-sotalol and bretylium on normal and ischaemic Purkinje fibres one day after ligation of canine left anterior descending coronary artery. In ischaemic Purkinje fibres superfused with normal Tyrode's solution (4mM K+, 2.7mM Ca+2) clofilium produced early afterdepolarisations at 10(-7)M and 10(-6)M, d-sotalol at 10(-5)M to 10(-3)M, and bretylium at 10(-3)M. The early afterdepolarisation response of ischaemic tissue, which in some cases prolonged action potential duration to beyond 10 s, was significantly different from the simple prolongation of action potential duration seen in normal Purkinje fibres at the same concentrations. Clofilium and d-sotalol differentially produced early afterdepolarisations at or very near "anti-arrhythmic" doses. Therefore, class III anti-arrhythmics produced early afterdepolarisations differentially in ischaemic tissue at concentrations which did not produce early afterdepolarisations in normal tissue.

Animals↗

Dependence of delayed afterdepolarizations on diastolic potentials in ischemic Purkinje fibers.

The mechanism of focal rhythms 1 day after myocardial infarction has been ascribed to both abnormal automaticity and triggered activity arising from delayed after-depolarizations (DADs). During the course of superfusion in vitro, diastolic potentials repolarize to more negative resting potentials. The dependence of DADs and triggered activity on diastolic potentials was studied using extrinsic currents. During sustained activity (maximum diastolic potential = -61 +/- 7 mV), hyperpolarizing current decreased the DADs, rendered them subthreshold, and terminated triggered activity. During the quiescence caused by constant hyperpolarizing current, a stimulated train of action potentials produced DADs. Decreasing the current permitted augmented DADs. In quiescent preparations (resting potential = -68 +/- 7 mV), a train of stimulated action potentials was followed by subthreshold DADs. Depolarizing current increased the DAD amplitude. To exclude depolarization-induced automaticity, constant currents were applied without a previous train of stimuli. Neither DADs nor triggered activity were evoked. Therefore, DADs and triggered activity, postinfarction, depend on the diastolic potential. There is a continuity between subthreshold DADs and sustained activity. DADs may reach a magnitude in which extrinsic interventions may not adequately terminate sustained triggered activity.

Action Potentials↗

Value of the signal-averaged electrocardiogram as a predictor of the results of programmed stimulation in nonsustained ventricular tachycardia.

A prospective assessment of several clinical variables, left ventricular function indexes, Holter recording characteristics and signal-averaged electrocardiogram (ECG) for their value in predicting the inducibility of sustained ventricular tachyarrhythmias was carried out in a consecutive series of 105 patients with nonsustained ventricular tachycardia (VT). The patients were divided into 3 groups based on the results of programmed electrical stimulation: group 1, 22 patients with induced sustained monomorphic VT; group 2, 14 patients with induced ventricular fibrillation (VF) and group 3, 69 patients with no induced sustained VT/VF. Left ventricular ejection fraction less than 0.40, history of syncope/presyncope and abnormal signal-averaged ECG were significantly more common in group 1 than in group 3. No significant difference was found between groups 2 and 3. The sensitivity, specificity and predictive accuracy of the signal-averaged ECG for the induction of sustained monomorphic VT were 64, 89 and 84%, respectively. Using stepwise discriminant function analysis, the signal-averaged ECG was found to be the single most accurate screening test to predict the inducibility of sustained VT in patients with nonsustained VT and its value was independent of the etiology of heart disease and the length of spontaneous runs. Because of the very high specificity and negative predictive accuracy, patients with normal signal-averaged ECGs may not require invasive evaluation.

Cardiac Pacing, Artificial↗

Preservation of left ventricular function in patients with total occlusion of the left anterior descending coronary artery and wide-caliber distal vessel filling by collateral vasculature.

The segmental ventricular function of 76 patients with total occlusion of the left anterior descending coronary artery (LAD) was analyzed to establish the relationship between ventricular function and the presence and angiographic appearance of the collateral circulation. The relationship between function and collateral supply was found to be significant (P less than .01). The only angiographic feature of the collateral vasculature that was associated with preserved function was the caliber of the distal LAD. Wide-caliber vessels were more likely to be associated with preserved ventricular function than thin vessels (P less than .01). In contrast, both rapidly filling collateral arteries and slow filling vessels were associated with preserved ventricular function. Collateral supply maintenance was significantly associated with preserved ventricular function, even when the collaterals arose from stenotic coronary arteries. Furthermore, despite marked differences in ventricular function between the base and apex of the heart, there was a true relationship between preserved ventricular function and the presence of collateral vessels for all segments of the anterior wall. These findings may be relevant to clinical decision making and to proper interpretation of studies of ventricular function following LAD occlusion.

Angiography↗

Stretch activated ion channels in ventricular myocytes.

Patch-clamp recordings from ventricular myocytes of neonatal rats identified ionic channels that open in response to membrane stretch caused by negative pressures (1 to 6 cm Hg) in the electrode. The stretch response, consisting of markedly increased channel opening frequency, was maintained, with some variability, during long (greater than 40 seconds) stretch applications. The channels have a conductance averaging 120pS in isotonic KCl, have a mean reversal potential 31 mV depolarized from resting membrane potential, and do not require external Ca++ for activation. The channels appear to be relatively non-selective for cations. Since they are gated by physiological levels of tension, stretch-activated channels may represent a cellular control system wherein beat-to-beat tension and/or osmotic balance modulate a portion of membrane conductance.

Animals↗

Effects of clofilium on ischemic subendocardial Purkinje fibers 1 day postinfarction.

One day after ligation of the canine anterior descending coronary artery, clofilium, a long-acting class III antiarrhythmic agent, was studied for its effects on normal and ischemic Purkinje fibers. In normal Tyrode's solution (4 mM potassium, 2.7 mM calcium) clofilium (10(-7) to 10(-5) M) increased action potential duration. Although only 2 of 10 normal Purkinje fibers developed early after depolarizations and early afterdepolarization-initiated triggered activity, 10 of 11 ischemic Purkinje fibers developed these features. Consequently, action potentials in ischemic fibers were prolonged to durations greater than 10 s. The triggered activity in the ischemic Purkinje fibers produced repetitive activity in adjacent normal ventricular muscle. In vivo, 3 days after ligation, the administration of 3 to 10 mg/kg clofilium induced grouped beating. Action potentials recorded subsequently from these same hearts in vitro showed early afterdepolarizations, triggered activity and a similar grouping of responses. Therefore, clofilium differentially produced early afterdepolarizations in ischemic Purkinje fibers. This is a mechanism by which clofilium could be arrhythmogenic in an ischemic heart.

Action Potentials↗

DDD-pacemaker pseudomalfunction during supraventricular tachycardia.

Asynchronous pacing during the presence of electromagnetic interference or other sources of "noise" is a protective mechanism available to prevent pacemaker output inhibition. We describe a patient with a DDD pacemaker who had asynchronous dual chamber or noise reversion pacing as a consequence of repetitive signals (QRS complexes) falling into the noise sampling period (NSP) of the pacemaker ventricular refractory period. During supraventricular tachycardia at a rate of 215 bpm, noise reversion mode pacing occurred when QRS complexes were well detected immediately after the termination of a normal pacemaker ventricular refractory period and treated as a premature ventricular depolarization, resulting in automatic refractory period extension. Recycling of this extended refractory period occurred when consecutive QRS complexes were detected during the NSP and forced asynchronous dual chamber pacing at the programmed lower rate. The mechanism is presented and was supported by subthreshold esophageal pacing simulating the tachycadia and initiating the noise reversion response.

Cardiac Pacing, Artificial↗

Initiation of ventricular fibrillation by supraventricular beats in patients with acute myocardial infarction.

The role of supraventricular extrasystoles in the initiation of ventricular arrhythmia was studied in 72 consecutive patients who developed primary ventricular fibrillation during the acute phase of myocardial infarction. In six patients (8%), a total of 12 episodes of ventricular fibrillation and 16 episodes of ventricular tachycardia were initiated by supraventricular extrasystoles. Ventricular fibrillation and tachycardia were initiated by single supraventricular extrasystoles in 16 and by salvos greater than or equal to two beats in 12 episodes. The RR coupling interval of the supraventricular impulse immediately preceding ventricular tachycardia ranged from 240 to 420 ms (mean 356 (62)) and was characteristic of R-on-T (prematurity index less than 1) in 63% of episodes. Average peak serum creatine kinase activity in the six patients in whom ventricular tachycardia was initiated by a supraventricular extrasystole was 1275 units compared with 720 units in the remaining 66 patients. Five of these six patients later showed evidence of pump failure. Lignocaine or procainamide or both suppressed the ventricular arrhythmia in five of the six patients. The initiation of ventricular fibrillation or tachycardia by supraventricular extrasystoles in acute myocardial infarction is not uncommon and may reflect the increased vulnerability of the heart after a large infarct. These arrhythmias may respond to drugs that suppress ventricular irritability.

Cardiac Complexes, Premature↗

Time course of ventricular arrhythmias and the signal averaged electrocardiogram in the post-infarction period: a prospective study of correlation.

The incidence and time course of complex ventricular arrhythmias and of the abnormal signal averaged electrocardiogram were studied prospectively in 90 patients in the first two months after acute myocardial infarction. Serial recordings of both 24 hour ambulatory and signal averaged electrocardiograms were obtained 0-5 days (phase 1), 6-30 days (phase 2), and 31-60 days (phase 3) after infarction. A total of 264 ambulatory electrocardiograms and 264 signal averaged electrocardiograms were available for analysis. Complex ventricular arrhythmias were seen in 31%, 17%, and 38% of patients during phases 1, 2, and 3 respectively, and abnormal signal averaged electrocardiogram in 13%, 24%, and 16%. The incidence of complex ventricular arrhythmias was not significantly different in patients with or without an abnormal signal averaged electrocardiogram in the entire study period nor in any of the three phases after infarction. During phase 2 when abnormal signal averaged electrocardiograms were most common complex ventricular arrhythmias were least common. This lack of correlation suggests that the abnormal signal averaged electrocardiogram and complex ventricular arrhythmias after infarction have different electrophysiological bases.

Adult↗

Reentrant ventricular rhythms in the late myocardial infarction period: prevention of reentry by dual stimulation during basic rhythm.

Stimulation at two ventricular sites during basic rhythm as a means of preventing the induction of ventricular arrhythmias in the postinfarction heart was investigated. Isochronal maps of ventricular epicardial activation from dogs were analyzed 4 days after ligation of the left anterior descending coronary artery. Activation patterns were obtained by use of a computerized data acquisition system recording from 62 sites. Effective refractoriness and conduction time during basic paced rhythm (S1) for each site were summed to construct isochronal maps of recovery time. The patterns of recovery time on the heart were eccentrically layered, with a narrow zone of differentially prolonged recovery time along one border of the infarct. The formation of an arc of functional conduction block after premature stimulation (S2) was correlated with regions of differentially prolonged recovery time (59 +/- 30 msec, mean +/- SD) between recording sites spaced 5 to 10 mm apart. The recovery time difference between sites that did not block (17 +/- 14 msec) was significantly shorter. The spatial distribution of recovery time on the heart could be modified by application of stimuli at two sites during the basic rhythm. Reentry was prevented by appropriate placement of the secondary site in the ischemic zone and the temporal sequencing of the paired stimuli. Stimulation at the secondary site "peeled back" refractoriness in the ischemic zone. Prevention of reentry was a result of either: (1) a shift in the arc of conduction block toward the ischemic zone, (2) a reduction in the extent of the continuous arc, (3) early activation of regions distal to the arc, or (4) a combination of the above. In two dogs, the arc of block was abolished entirely after dual stimulation. This report illustrates the criteria for effective prevention of reentry, applied to a well-described verifiable model of reentrant activation.

Animals↗

QTU prolongation and polymorphic ventricular tachyarrhythmias due to bradycardia-dependent early afterdepolarizations. Afterdepolarizations and ventricular arrhythmias.

Polymorphic ventricular tachyarrhythmias occurred spontaneously during bradycardia in dogs given the inotropic polypeptide anthopleurin-A (AP-A). The arrhythmia was investigated in in vitro and in vivo experiments. In in vitro experiments, AP-A (50 micrograms/l) produced bradycardia-dependent prolongation of action potential duration that was more pronounced in Purkinje than in muscle fibers. Only Purkinje fibers developed early afterdepolarizations (EAD) and triggered activity. These effects could be abolished by rapid pacing, lidocaine (4 mg/l), or tetrodotoxin (1 mg/l). In vivo experiments were conducted in anesthetized healthy dogs with simultaneous recording of surface ECG, monophasic action potentials from the endocardial and epicardial surface of the left ventricle by contact electrode catheter technique, and transmembrane action potentials from the epicardial surface of the left ventricle with a floating microelectrode technique. AP-A in a dose comparable to that used in vitro (4 micrograms/kg, i.v. bolus) resulted in bradycardia-dependent marked prolongation of both monophasic and transmembrane action potentials. An EAD gradually appeared on both recordings but was more marked in endocardial monophasic action potentials. Eventually, a premature ventricular depolarization arose from or very close to the peak of the EAD. The prolongation of action potentials was associated with similar prolongation of the QTU interval in surface ECG, and in some experiments, the EAD corresponded to a distinct prominent U wave. A ventricular premature depolarization arose from the U or TU complex and initiated polymorphic ventricular tachyarrhythmias that terminated spontaneously or degenerated into ventricular fibrillation. These effects were reversed by rapid pacing or lidocaine (1 mg/kg). The present study provides evidence in support of the hypothesis that AP-A-induced ventricular tachyarrhythmias are due to bradycardia-dependent EAD and triggered activity.

Action Potentials↗

Risk stratification of patients with complex ventricular arrhythmias. Value of ambulatory electrocardiographic recording, programmed electrical stimulation and the signal-averaged electrocardiogram.

Currently, there are three prognostic indicators of ventricular electrical instability: long-term ambulatory ECG recording, programmed electrical stimulation and the signal-averaged electrocardiogram. Several clinical studies have suggested that frequent and complex ventricular premature contractions in patients with organic heart disease may identify future cardiac events, including sudden cardiac death although, with respect to prognosis, it is not likely that any grading system based on the ambulatory ECG will be without meaningful limitations. No study has adequately tested the hypothesis that decreasing ventricular arrhythmias after acute myocardial infarction reduces mortality. The inducibility of ventricular tachycardia during programmed electrical stimulation is regarded as an independent risk factor for sudden death. Predominantly due to the lack of standardized protocol and definitions, the actual relevance of current literature remains somewhat compromised. The indication for antiarrhythmic treatment in those patients in whom ventricular tachycardia can be induced has not been established with certainty since the effects of therapy on the prognosis are unknown. For patients with complex ventricular arrhythmias in whom sustained ventricular tachycardia cannot be induced, antiarrhythmic drug treatment does not appear indicated. Based on a number of studies, the presence of late potentials in the signal-averaged ECG has also been shown to be a meaningful prognostic indicator. The signal-averaged ECG, however, is not only subject to various technical problems but is also encumbered by limitations arising from electrophysiologic considerations. While no relationship could be established between late potentials and complex ventricular arrhythmias in the ambulatory ECG within the first two months after acute myocardial infarction, there was, however, a correlation between late potentials and the inducibility of ventricular tachycardia during programmed electrical stimulation. Consequently, the signal-averaged ECG may serve as a screening test to identify patients who should subsequently undergo programmed electrical stimulation for arrhythmia assessment or guided institution of treatment provided this proves to be effective in reducing the risk of future major arrhythmic events.

Cardiac Complexes, Premature↗

Effects of analyzed signal duration and phase on the results of fast fourier transform analysis of the surface electrocardiogram in subjects with and without late potentials.

A microcomputer-based system capable of performing time- and frequency-domain analysis on the same set of acquired and signal-averaged raw data was used to correlate late potentials detected in the time domain with the results of frequency-domain analysis. Ten patients with spontaneous or inducible sustained ventricular tachycardia (VT) known to have abnormal late potentials in the time-domain signal-averaged electrocardiogram and 10 normal subjects without late potentials were studied. Fast Fourier transform analysis was performed on a segment that comprised the last 40 ms of the QRS and the ST segment up to the onset of the T wave as identified visually. The high-frequency signal content, expressed as the area ratio or the peak magnitude, was found to be markedly dependent on the length of the analyzed QRS-ST segment. A change of as little as 3 ms in the duration of the estimated QRS-ST segment changed the results of the frequency analysis across proposed boundaries of normalcy in normal subjects and in patients with VT. This resulted in both false-negative and false-positive conclusions. Similar results were obtained when the effects of varying analyzed signal length or phase were studied using a pure synthesized sine wave signal. For frequency analysis to be clinically useful and reproducible, standards of normalcy must be established for a signal region of fixed duration or the technique must be modified so as to be insensitive to duration of signal sample.

Adult↗