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N el-Sherif

Publications and source records attributed to N el-Sherif.

At least 37 records · Page 2Linked to original sources

Activation time determination by high-resolution unipolar and bipolar extracellular electrograms in the canine heart.

INTRODUCTION: To identify the optimal criteria for activation time (AT) determination of bipolar electrograms from normal hearts, a high-resolution cross electrode array comprising 128 unipolar electrodes of 500-microns spacing was used to record extracellular potentials from the left ventricular epicardium of 12 dog hearts. METHODS AND RESULTS: Recordings were made during broad wavefront propagation (B wave) and local elliptical wavefront propagation (E wave). Characteristics of 863 bipolar electrograms (1-mm spacing) were constructed from unipolar data standardized for differences in polarity, then classified morphologically. Features for bipolar AT determination were compared to the time of the negative peak of the first temporal derivative of a unipolar electrogram situated mid-way between the bipoles. During B wave, three distinct morphologies were observed: uniphasic (61%), biphasic (23%), and triphasic (16%). Peak voltage of uniphasic and triphasic signals was the best predictor of AT (error: 0.6 +/- 0.6 msec and 0.6 +/- 0.8 msec, respectively). During E wave, parallel orientation of the bipoles with respect to the direction of impulse propagation wavefront resulted in uniphasic signals (> 99%), while for perpendicular orientation of the bipoles, electrogram morphology was variable. For parallel orientation of the bipoles, peak negative voltage was the best predictor of AT for both longitudinal and transverse propagation, while for perpendicular bipole orientation, peak negative voltage was a less reliable predictor for propagation along both fiber axes. Increasing interpolar distance resulted in a degradation in AT accuracy for B wave (from 0.6 +/- 0.6 msec at 1 mm to 1.1 +/- 1.2 msec at 7 mm) and for E wave (from 0.4 +/- 0.3 msec at 1 mm to 3.1 +/- 2.9 msec at 7 mm). CONCLUSIONS: (1) The accuracy of bipolar electrograms is sensitive to wavefront direction, bipole orientation, and interpolar distance; (2) peak negative voltage of uniphasic and triphasic signals is a reliable predictor of AT, but only for B wave; (3) a maximum interpolar distance of 2 mm and bipole orientation parallel to the direction of the impulse wavefront are minimally required for accurate determination of AT during impulse propagation initiated near the recording electrodes; and (4) for impulses initiated near the recording site in normal tissue, a biphasic or triphasic morphology almost certainly indicates that the bipolar electrode is oriented perpendicular to the wavefront direction, irrespective of fiber orientation.

Action Potentials↗

Risk stratification for arrhythmic events in patients with nonischemic dilated cardiomyopathy and nonsustained ventricular tachycardia: role of programmed ventricular stimulation and the signal-averaged electrocardiogram.

OBJECTIVES: This study investigated prediction of arrhythmic events by the signal-averaged electrocardiogram (ECG) and programmed stimulation in patients with nonischemic dilated cardiomyopathy. BACKGROUND: Risk stratification in patients with nonischemic dilated cardiomyopathy remains controversial. METHODS: Eighty patients with nonischemic dilated cardiomyopathy and spontaneous nonsustained ventricular tachycardia underwent signal-averaged electrocardiography (both time-domain and spectral turbulence analysis) and programmed stimulation. All patients were followed up for a mean of 22 +/- 26 months. RESULTS: Sustained monomorphic ventricular tachycardia was induced in 10 patients (13%), who all received amiodarone. The remaining 70 patients were followed up without antiarrhythmic therapy. Of the 80 patients, 15% had abnormal findings on the time-domain signal-averaged ECG, and 39% had abnormal findings on spectral turbulence analysis. Time-domain signal-averaged electrocardiography had a better predictive accuracy for induced ventricular tachycardia than spectral turbulence analysis (88% vs. 66%, p < 0.01). During follow-up, there were 9 arrhythmic events (5 sudden deaths, 4 spontaneous ventricular tachycardia/fibrillation) and 10 nonsudden cardiac deaths. Cox regression analysis showed that no variables predicted arrhythmic events or total cardiac deaths. The 2-year actuarial survival free of arrhythmic events was similar in patients with or without abnormal findings on the signal-averaged ECG or induced ventricular tachycardia. CONCLUSIONS: In patients with nonischemic dilated cardiomyopathy, 1) there is a strong correlation between abnormal findings on the time-domain signal-averaged ECG and induced ventricular tachycardia, but both findings are uncommon; and 2) normal findings on the signal-averaged ECG, as well as failure to induce ventricular tachycardia, do not imply a benign outcome.

Actuarial Analysis↗

Prognostic significance of signal-averaged electrocardiogram after thrombolytic therapy and/or angioplasty during acute myocardial infarction (CAST substudy). Cardiac Arrhythmia Suppression Trial (CAST) SAECG Substudy Investigators.

Thrombolytic therapy and angioplasty during the early phase of an acute myocardial infarction (AMI) have been shown to improve prognosis. Time-domain analysis of the signal-averaged electrocardiogram (SAECG) provides strong, independent prediction of arrhythmic events (arrhythmic death/resuscitated cardiac arrest) after AMI. To determine whether the prognostic significance of an abnormal SAECG (QRS duration > or = 120 ms) measured after AMI is influenced by thrombolytic therapy/angioplasty given in the AMI period, the predictive value of SAECG was compared in patients with and without prior thrombolysis/angioplasty in a substudy of the Cardiac Arrhythmia Suppression Trial. Information was available in 787 patients. The average follow-up was 10 +/- 3 months and arrhythmic events occurred in 33 patients (4.2%). The prevalence of abnormal SAECG in patients with and without thrombolytic therapy/angioplasty was 9.4% (34 of 363 patients) and 14.9% (63 of 424 patients), respectively (p < 0.02). The arrhythmic event rate for patients with abnormal SAECG with and without thrombolytic therapy/angioplasty was 20.6% (7 of 34 patients) and 20.6% (13 of 63 patients), respectively. The arrhythmic event rate for patients with normal SAECG with and without thrombolytic therapy/angioplasty was 0.9% (3 of 329 patients) and 2.8% (10 of 361 patients), respectively. It is concluded that in patients with an AMI (1) the use of thrombolytic therapy/angioplasty is associated with a significantly decreased prevalence of abnormal SAECG, (2) thrombolytic therapy/angioplasty associated with a normal SAECG portends an excellent prognosis, and (3) an abnormal SAECG is predictive of an increased incidence of arrhythmic events in all patients regardless of prior thrombolytic therapy/angioplasty.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Incidence and prediction of induced ventricular tachyarrhythmias in idiopathic dilated cardiomyopathy.

The value of time-domain and spectral turbulence analyses of the signal-averaged electrocardiogram (SAECG) for predicting induction of sustained monomorphic ventricular tachycardia (VT) was prospectively investigated in 70 patients with idiopathic dilated cardiomyopathy. Sustained VT was induced in 9 patients (13%). The prevalence of abnormal time-domain and spectral analyses was 16 and 37%, respectively. The total predictive accuracy of time-domain and spectral analyses for VT induction was 86 and 67%, respectively (p < 0.01). The predictive accuracy of time-domain and spectral analysis was similar in patients without an intraventricular conduction defect (94 and 84%, respectively). However, the predictive accuracy of time-domain was higher than that of spectral analysis in patients with an intraventricular conduction defect (65 vs 25%; p < 0.05). The poor concordance between spectral analysis and programmed stimulation results was mainly due to the high number of false-positive recordings in the presence of an intraventricular conduction defect (9 of 20 cases). With the use of stepwise discriminant function analysis, an abnormal time-domain SAECG was the only variable predicting the induction of sustained VT (p < 0.0003). In dilated cardiomyopathy, an abnormal time-domain SAECG and induced sustained VT are rare, both time-domain signal-averaged electrocardiography and spectral analysis have a high predictive accuracy for VT induction in patients without an intraventricular conduction defect, and spectral analysis does not improve VT prediction in those with a conduction defect.

Analysis of Variance↗

Circus movement atrial flutter in the canine sterile pericarditis model. Relation of characteristics of the surface electrocardiogram and conduction properties of the reentrant pathway.

OBJECTIVES: This study was designed to elucidate the basis for the electrocardiographic (ECG) appearance of atrial flutter in the canine sterile pericarditis model. BACKGROUND: During atrial flutter, the surface ECG may show typical F waves or isolated P waves of any polarity. METHODS: Electrocardiographic leads II, III and aVF and epicardial atrial activation maps constructed from 127 simultaneously recorded bipolar electrograms were compared in 20 dogs with sterile pericarditis and inducible atrial flutter. RESULTS: In 10 dogs with F wave atrial flutter, single loop reentry occurred around combined functional/anatomic obstacles that included one or both caval veins and a vertically oriented arc of functional conduction block. In 10 dogs with P wave atrial flutter, a merely functional (n = 4) or combined (n = 6) obstacle involving any atrial vessel and more vertically (n = 5) or more horizontally (n = 5) oriented arcs of block was present. The isoelectric interval between P waves corresponded to the conduction time within the slow zone of the reentrant circuit (96 +/- 27 vs. 100 +/- 24 ms, mean +/- SD). Slow conduction accounted for 65 +/- 8% of the cycle length in P wave atrial flutter, but for only 29 +/- 7% in F wave atrial flutter (p < 0.05). Slow conduction was usually associated with activation of fewer than five epicardial electrodes per 10-ms isochronal interval, reflecting only a small amount of atrial tissue. The polarity of P or F waves was determined by the direction of the major wave front activating the most electrodes per 10-ms isochronal interval, irrespective of whether the right or the left atrium was activated. CONCLUSIONS: The F waves result from reentrant activation at a relatively constant speed around a vertically oriented functional/anatomic obstacle involving one or both caval veins. The P waves occur when the circuit contains a marked area of slow conduction.

Animals↗

Combined time-domain and spectral turbulence analysis of the signal-averaged ECG improves its predictive accuracy in postinfarction patients.

The predictive accuracy of time-domain (TD) late potential analysis of the signal-averaged electrocardiogram in postmyocardial infarction (MI) is limited by the high incidence of false positives in inferior MI. However, frequency-domain spectral turbulence (ST) analysis suffers from a high incidence of false positives, especially in anterior MI. A prospective study was conducted of 262 patients with acute MI to investigate the hypothesis that combined TD and ST analyses of the signal-averaged electrocardiogram could improve its predictive accuracy for serious arrhythmic events in the post-MI period. Abnormal TD criteria were RMS40 less than 25 microV at 25 Hz plus RMS40 less than 16 microV at 40 Hz, and abnormal ST criteria were a turbulence score of 3 or 4. Seventeen patients had arrhythmic events during 10.5 +/- 2.4 months of follow-up evaluation (13 sudden cardiac death judged to be due to arrhythmia and 4 nonfatal sustained ventricular tachycardia). The total predictive accuracy of combined TD and ST (92%) was higher than TD (87%), whereas ST had the lowest total predictive accuracy of 78%. The negative predictive accuracy of all three analyses was high (96-97%). However, the positive predictive accuracy of TD (28%) was higher than ST (14%). Combined TD and ST significantly improved the positive predictive accuracy of the test to 35% in the total group and to 40% in patients with first anterior or inferior MI. The best results were obtained in patients with first anterior MI, where the positive predictive accuracy of combined analysis was 50%.

Arrhythmias, Cardiac↗

Time-domain and frequency-domain analyses of the signal-averaged ECG in patients with ventricular tachycardia and ischemic versus nonischemic dilated cardiomyopathy.

The value of time-domain and frequency-domain (spectral turbulence) analyses of the signal-averaged electrocardiogram was investigated to predict induced sustained monomorphic ventricular tachycardia (VT). Two groups of patients with spontaneous nonsustained VT and left ventricular ejection fraction less than 50% were enrolled: 70 patients with idiopathic dilated cardiomyopathy (group 1) and 70 patients with ischemic heart disease (group 2). Sustained VT was induced in 9 cases (13%) in group 1 and 16 (23%) in group 2. The prevalence of abnormal time-domain and spectral turbulence analysis was 16 and 37%, respectively, in group 1 and 27 and 51%, respectively, in group 2 (NS). In group 1, the predictive accuracy of time-domain and spectral turbulence analysis for induced VT was 86 and 67%, respectively (P < .01). In group 2, the predictive accuracy of the two techniques for induced VT was, respectively, 79 and 66% (NS). In both groups, the predictive accuracy of time-domain analysis was higher than that of spectral turbulence analysis in patients with intraventricular conduction defect (IVCD): 65 versus 25%, respectively, in group 1 (P < .01), and 81 versus 44%, respectively, in group 2 (P < .05). However, the predictive accuracy of time-domain and spectral analyses was similar in patients without IVCD: 94 versus 84%, respectively, in group 1, and 77 versus 74%, respectively, in group 2. Thus, in patients with dilated cardiomyopathy, (1) the etiology does not affect the predictive accuracy of time and frequency domain and frequency-domain analyses have high predictive accuracy in patients without IVCD; and (3) spectral turbulence analysis does not improve VT prediction in patients with IVCD.

Cardiac Pacing, Artificial↗

A logical state model of circus movement atrial flutter role of anatomic obstacles, anisotropic conduction and slow conduction zones on induction, sustenance, and overdrive paced modulation of reentrant circuits.

Mapping studies of atrial flutter in both the canine sterile pericarditis model and the right atrial enlargement model commonly reveal single loop reentrant circuits in the lower posterior part of the right atrium. Functional bidirectional conduction block and natural anatomical obstacles comprise the central obstacle for reentrant impulse during circus movement atrial flutter. Because the relative roles of anatomical obstacles, in combination with functional barriers, anisotropic conduction, and slow conduction can not be readily assessed with current electrophysiological techniques, an atrial activation model was developed to study the mechanisms of circus movement atrial flutter. A discrete state model consisting of 4096 logically connected cardiac elements was used to simulate atrial activation; an inexcitable region simulating the inferior vena cava (IVC) was also incorporated in the model. Atrial flutter was induced by programmed premature stimulation. Anisotropic conduction velocity properties, regional variations in slow conduction, regional refractory gradients and stimulation parameters were specified for each simulation. The reentrant circuit generally consisted of a single reentrant impulse which circulated around a continuous line of functional bidirectional conduction block joined to the IVC. Rapid pacing, 5-30 ms shorter than the spontaneous reentrant cycle length, was applied to entrain and/or terminate the rhythm. The results of this study demonstrate that patterns of initiation, entrainment, termination and reinitiation of circus movement atrial flutter mimic results from in vivo activation mapping studies. We find that sustained circus movement atrial flutter circuits depend on: 1) natural anatomical obstacles to stabilize reentrant circuits, and 2) anisotropic conduction properties to reduce the degree of functional conduction block needed to maintain circus movement. Rapid pacing of simulated circus movement atrial flutter demonstrated that the entrainment criteria can be satisfied in a two-dimensional syncytium.

Animals↗

Early afterdepolarization formation in cardiac myocytes: analysis of phase plane patterns, action potential, and membrane currents.

INTRODUCTION: Early afterdepolarizations (EADs) are among the mechanisms proposed to underlie ventricular arrhythmias. Sea anemone toxin, ATXII, known to delay Na inactivation and to induce plateau level voltage oscillations, was used to study the formation of EADs. METHODS AND RESULTS: Action potential and membrane currents were studied in rat ventricular myocytes using whole cell current and voltage clamp techniques. Phase plane trajectories were generated by plotting membrane potential (V) versus the first time derivative of membrane potential (dV/dt). Under current clamp conditions, ATXII (40 nM) consistently prolonged the action potential and induced EADs. The EADs developed at a plateau voltage between -10 and -40 mV. Calcium channel blockers, verapamil 10 microM and cobalt 4 mM, and the sarcoplasmic reticulum modulator, ryanodine (1 microM), did not antagonize ATXII effects on the action potential and EADs. However, Na channel blockers, tetrodotoxin 0.3 microM and lidocaine 40 microM, and rapid stimulation consistently shortened the prolonged action potential and suppressed EADs. Under voltage clamp conditions in the presence of ATXII, a slowly decaying inward current followed the fast inward current during depolarizing pulses. Membrane currents flowing at or later than 100 msec after the test pulse were analyzed. The control isochronal current-voltage (I-V) curves showed no late inward currents. In the presence of ATXII, all the isochronal I-V curves showed an inward current that was more prominent between -40 and 0 mV. The ATXII-induced current at the 100-msec isochrone activated at a potential of approximately -60 mV, peaked at about -20 mV, and reversed at +40 mV consistent with the Na current I-V curve. The isochronal I-V curves obtained after lidocaine superfusion resembled those of the control. The phase plane trajectory of the action potential obtained with ATXII showed an oscillatory behavior corresponding to the EAD range of potential; within this voltage range, the isochronal I-V curves were shown to cross the abscissa three times instead of once. CONCLUSION: These results suggest that, in this experimental model, neither sarcolemmal L-type Ca current nor sarcoplasmic reticulum Ca release plays a significant role in the genesis of ATXII-induced EADs. EADs are generated by a voltage-dependent balance between a markedly prolonged Na inward current and K outward currents within the voltage plateau range of the action potential but not by Ca current reactivation and inactivation.

Action Potentials↗

Ketanserin inhibits depolarization-activated outward potassium current in rat ventricular myocytes.

Ketanserin (KT), an antihypertensive agent, has been shown to prolong action potential duration (APD) and QT interval and to induce torsade de pointes in some patients. We previously suggested that the prolongation of APD could be due to KT inhibition of the fast component of the delayed rectifier current (IKr) in guinea-pig myocytes. However, in other tissue such as human atrium, Purkinje fibers, epicardial cells, and rat ventricular myocytes, the transient outward potassium current (Ito) is one of the major repolarizing currents. We investigated the possibility that KT could also increase APD by blocking Ito. Action potentials and membrane currents were recorded from rat ventricular myocytes known to have a large Ito by using whole-cell patch-clamp techniques. We found that KT (50 mumol/L) significantly prolonged APD at 50% repolarization by 218% (P < .05) and APD at 90% repolarization by 256% (P < .05) with no significant effect on other action potential parameters. Time-dependent Ito and sustained current (ISus) were measured in the presence of 400 nmol/L nisoldipine during depolarizing pulses to 40 mV from a holding potential of -100 mV every 10 seconds. KT resulted in a concentration- and time-dependent inhibition of charge area of Ito evaluated by integration with an EC50 of 8.3 mumol/L. The inhibitory effect of KT (10 mumol/L) was seen at voltages from 0 to 80 mV without any shift of the current-voltage relation of peak Ito. KT did not significantly change activation, inactivation, and reactivating curves of Ito. Kinetic analysis of Ito showed a biexponential fit of inactivation in 80.5% of total tracings studied at voltages between -30 and 80 mV (n = 149, R = .99 +/- .01). The inhibitory effect of KT was more prominent on charge areas of the slow component (Qs) than the fast component (Qf) of Ito (Qf = 33.2 +/- 6.2 s.pA and Qs = 235.5 +/- 7.4 s.pA for the control condition; 12.4 +/- 4.3 and 59.6 +/- 17 s.pA for KT at 40 mV; n = 4). The binding association (k) and dissociation (l) constants at 40 mV were 9.0 +/- 0.9x10(6) M-1.s-1 and 86.6 +/- 0.3 s-1, respectively. KT also blocked ISus in a dose-dependent manner with an EC50 of 11.2 mumol/L and had no significant effect on both the inward rectifier potassium current and the L-type calcium current.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

Recurrent syncope for over a decade due to idiopathic ventricular fibrillation.

A 35-year-old man had a history of recurrent syncope for more than a decade. During a witnessed episode, an ambulatory electrocardiographic recording showed ventricular flutter/fibrillation that lasted for 2 1/2 minutes and terminated spontaneously without adverse neurologic sequelae. No structural heart disease and no possible etiologic factor for the ventricular tachyarrhythmia was found. The patient received an automatic implantable cardioverter defibrillator. Review of the literature suggests that the automatic implantable cardioverter defibrillator is a valid option in idiopathic ventricular fibrillation in young individuals to avoid the potential risk of recurrent cardiac arrest.

Adult↗

Reduction of ischemia-induced electrophysiologic abnormalities by glucose-insulin infusion.

OBJECTIVES: This study was designed to determine the effects of glucose-insulin infusion on ischemia-induced changes in extracellular potassium ([K+]o) accumulation and the associated electrophysiologic abnormalities in the canine heart. BACKGROUND: Although glucose-insulin-potassium infusion has been shown to limit myocardial injury in acute ischemia, its effect on ischemia-induced electrophysiologic alterations has not been investigated. METHODS: Recordings of [K+]o and local electrograms from the normal, border and ischemic zones were obtained during serial (10-min) left anterior descending coronary artery occlusions in the control state and after infusion of glucose-insulin (eight dogs), glucose alone (six dogs) or insulin alone (eight dogs). RESULTS: Glucose-insulin infusion caused significant reduction in the rise of [K+]o during the entire period of ischemia in both ischemic and border zones associated with significant improvement in the degree of intramyocardial conduction delay. At 10 min of ischemia, [K+]o was reduced from a mean control level of 15.9 +/- 3.7 to 10.1 +/- 4.3 mmol/liter (p < 0.005) in the ischemic zone and from 6.8 +/- 1.9 to 5.5 +/- 1.1 mmol/liter (p < 0.05) in the border zone. The electrogram duration was shortened from a mean control value of 102 +/- 13 to 78 +/- 12 ms in the ischemic zone and from 79.2 +/- 7.8 to 58.1 +/- 6.6 ms in the border zone (p < 0.005). Glucose alone caused significant reduction in [K+]o during the initial 6 min of ischemia, only in the ischemic zone. Conversely, insulin caused no changes in [K+]o accumulation during ischemia. Neither glucose nor insulin alone had any effect on ischemia-induced intramyocardial conduction delay. CONCLUSIONS: The present study demonstrated that the combination of glucose and insulin is essential for the salutary effect of reducing [K+]o accumulation during ischemia and improving the associated intramyocardial conduction delay. It could be postulated that glucose in the presence of insulin increases the glycolytic flux, thereby providing adequate adenosine triphosphate for suppressing the cardiac adenosine triphosphate-sensitive potassium ion channels. The latter are, at least partially, responsible for the [K+]o rise in the early phase of ischemia. This study highlights the antiarrhythmic potential of interventions that modulate the metabolic consequences of ischemia.

Animals↗

A unified functional/anatomic substrate for circus movement atrial flutter: activation and refractory patterns in the canine right atrial enlargement model.

OBJECTIVES: This study was designed to test the concept of a functional/anatomic interaction in a canine model of reentry based on right atrial enlargement and to elucidate the electrophysiologic basis for functional conduction block. BACKGROUND: The monotonic feature of atrial flutter suggests a uniform substrate for the arrhythmia. Atrial flutter in the sterile pericarditis model is due to single-loop circus movement around a functional or a functional/anatomic obstacle near the atrioventricular (AV) ring. Sustained circus movement requires a critical interaction of a functional arc of block, a natural obstacle, the AV ring and a zone of slow conduction. The location of the inferior vena cava predisposes the lower right atrium to single-loop reentry. METHODS: In 11 dogs with right atrial enlargement, 127 bipolar epicardial electrograms were obtained during atrial flutter. For correlation of activation and refractory maps, the effective refractory period under each electrode was determined using the extrastimulus technique. RESULTS: Atrial flutter was due to single-loop reentry around functional arcs of block near the AV ring (n = 2) or around functional/anatomic obstacles (n = 8) involving the inferior vena cava. A slow zone was located between the arc and the AV ring and between the inferior vena cava and AV ring, respectively. During initiation, the arc joined the AV ring, forcing activation to proceed around the free end of the arc before breaking through the arc near the AV ring. Arrhythmia termination required the arc of block to rejoin the AV ring. Inducibility of sustained atrial flutter was associated with a marked spatial dispersion of refractoriness. The configuration of the functional arc of block was critically dependent on the spatial pattern of refractoriness. CONCLUSIONS: Atrial flutter requires a similar functional or functional/anatomic substrate independent of the underlying etiology. The spatial distribution of refractoriness in enlarged canine atria provides an adequate substrate for the development of functional conduction block.

Animals↗

Circus movement atrial flutter in the canine sterile pericarditis model. Cryothermal termination from the epicardial site of the slow zone of the reentrant circuit.

BACKGROUND: We have shown that atrial flutter (AF) in dogs with sterile pericarditis is commonly due to a single-loop reentrant circuit in the lower right atrium comprised of a functional or functional/anatomic obstacle and a slow zone of conduction (SZ) between the central obstacle and the atrioventricular (AV) ring. The goals of the present study were 1) to establish that the epicardial SZ is the critical component of circus movement AF and 2) to identify the optimal site within the epicardial SZ at which interruption of circus movement can be accomplished by ablative techniques. METHODS AND RESULTS: We analyzed the atrial activation patterns during epicardial cooling of the SZ with as N2O-cooled probe in eight dogs (five with clockwise [CW] reentrant circuit, one with counterclockwise [CCW] reentrant circuit, and two with both CW and CCW reentrant circuits around the same pathway). In all eight dogs, cooling (-5 to +5 degrees C for 5-20 seconds) the narrow isthmus at the inferoposterior part of the SZ between the central obstacle and the AV ring reversibly terminated the reentrant circuit, whereas cooling outside this area failed to terminate the reentrant circuit. The circus movement was not observed to continue along alternate pathways when conduction in this critical zone was interrupted. Both CW and CCW reentrant circuits could be terminated from the same site within the SZ. Cooling resulted in slowing of conduction in the SZ (55 +/- 15 msec) in both CW and CCW reentrant circuits. Cooling-induced termination of CW reentrant circuits was characteristically associated with oscillations of conduction in the cooled zone of the last three cycles before termination and conduction block occurred within the cooled zone. The last "manifest" reentrant cycle was associated with the longest conduction delay in the cooled zone. However, this delay was not necessarily reflected in the length of the last reentrant cycle because of compensatory acceleration of conduction in the rest of the pathway. On the other hand, in CCW reentrant circuits, conduction block occurred abruptly at the distal border of the SZ and without significant oscillations of conduction. CONCLUSIONS: The present study provides convincing evidence that single-loop circus movement in this model is critically dependent on an obligatory conduction in a SZ in the inferoposterior portion of the free right atrial wall between a functional obstacle and the AV ring. Because the atrial myocardium behaves electrophysiologically as a two-dimensional surface, the results of this study may help to guide the endocardial electrode catheter ablative technique for treatment of clinical AF.

Animals↗

Recordings from the slow zone of reentry during burst pacing versus programmed premature stimulation for initiation of reentrant ventricular tachycardia in patients with coronary artery disease.

Programmed premature stimulation and burst pacing were compared for initiation of ventricular tachycardia (VT) in 16 patients with inducible sustained monomorphic VT. In all patients VT could be induced by programmed stimulation with 2 or 3 extrastimuli. On the other hand, initiation of VT by burst pacing was dependent on the length of the train; only 2 to 4 of the 11 trains tested could induce VT in any single patient. Recordings obtained from the slow zone of reentry showed that programmed premature stimulation that induced VT resulted in a critical degree of conduction delay as revealed by lengthening of local fractionated electrograms spanning 70 to 100% of the diastolic interval. Similarly, the last beat of a burst pacing train that induced VT was always followed by a similar degree of local conduction delay, whereas trains that failed to induce VT were followed by a lesser delay. It is concluded that although programmed stimulation with up to 3 extrastimuli was consistently successful in inducing VT, burst pacing succeeded in only 26% of the trials and was dependent on the length of the train, which varied from one patient to the other. Similar to what was shown previously in the experimental model of reentrant VT, burst pacing could initiate, conceal, terminate, and reinitiate reentry depending on the length of the train.

Atrioventricular Node↗

Alpha 1- and beta-adrenergic interactions on L-type calcium current in cardiac myocytes.

We investigated the mechanism by which alpha 1-adrenergic activation regulates basal and stimulated whole cell L-type Ca current (ICa) in rat ventricular myocytes using the physiological neurotransmitter, norepinephrine (NE, 10 microM). Stimulation of alpha 1-adrenoceptors, achieved by NE + 10 microM esmolol (a beta-receptor antagonist), had no significant effect on basal ICa. alpha 1-adrenergic activation had a marked inhibitory effect on ICa elevated by beta activation (NE + 1 microM) prazosin, an alpha 1-receptor antagonist) or activation of adenylyl cyclase by forskolin (25 microM); the inhibitory effect was reversible upon washout. However, alpha 1-adrenergic stimulation had no significant effect on ICa previously increased by intracellular application of cAMP (25 microM). The inhibitory effect seen on ICa elevated by NE showed no significant shift of either I-V or inactivation curves. It is unlikely that the inhibitory effect of alpha 1-adrenergic stimulation on NE or forskolin-elevated ICa is mediated through activation of Ca-dependent protein kinase C or changes in intracellular free Ca (pCa = 8.5, EGTA 5 mM) or cAMP-dependent phosphodiesterase. We conclude that alpha 1-adrenergic inhibition of beta-adrenergic stimulated-ICa is probably mediated through an as yet unknown G-protein. This inhibitory effect could serve as a regulatory feedback mechanism in physiological and pathophysiological settings.

Adrenergic beta-Antagonists↗

TU alternans, long QTU, and torsade de pointes: clinical and experimental observations.

T or U wave alternans in association with long QTU and torsade de pointes (TdP) is uncommon and its mechanism(s) is unknown. We studied three patients with TU alternans, long QTU, and TdP: patient 1 was a newborn with congenital long QTU; patient 2 had marked hypokalemia and hypomagnesemia; and patient 3 was receiving procainamide. In the three patients, TU alternans was tachycardia dependent and preceded the onset of TdP. In the patient on procainamide, TU alternans and TdP occurred at long cardiac cycles. In this patient, endocardial monophasic action potential (MAP) recordings showed that TU alternans was associated with alternation of the duration of the plateau. A deflection consistent with early afterdepolarization (EAD) arose at a constant time interval from phase 0 but alternated from high and low levels of phase 3. The first ectopic beat of TdP arose on the descending limb of the EAD. TU alternans was investigated by MAP recordings in six normal dogs, following the administration of anthopleurin-A (AP-A), a drug shown to delay sodium inactivation and to induce bradycardia dependent long QTU, EADs, and TdP. In two dogs TU alternans was associated with 2:1 recordings of EAD and nearly constant plateau duration. In three dogs, TU alternans was associated with EAD that occurred in consecutive beats at constant time intervals from phase 0, but alternated from high and low phase 3 because of alternation of the duration of the plateau. In one dog, alternation of EAD and plateau duration occurred. In 36 separate episodes of TdP that were analyzed in the six dogs, 32 were bradycardia dependent but four developed on abrupt shortening of the cardiac cycle associated with alternation of action potential duration. Our results suggest: (1) TU alternans may be due to 2:1 propagation of an EAD or to alternation of the recovery kinetics of a repolarization current; (2) The constant occurrence of EAD in relation to phase 0 in spite of alternation of plateau duration suggests an ionic mechanism synchronized to depolarization; (3) Tachycardia dependent TdP in clinical and experimental examples of long QTU seems to be characteristically associated with TU alternans. Dispersion of repolarization may underlie the increased ventricular electrical instability in these cases.

Adult↗