Mechanism of facilitation of conduction in Purkinje fibers with sequential pacing

Clinical studies have demonstrated that retrograde conduction of a premature beat through the His-Purkinje system can be facilitated by atrioventricular sequential pacing. Several possible mechanisms of facilitation have been proposed. No studies, however, have shown the occurrence of this phenomenon or its mechanism in isolated Purkinje fibers. The present study demonstrated that facilitation of conduction of a premature beat can indeed occur in isolated canine Purkinje fibers during sequential pacing. When a premature beat showed conduction delay during unidirectional pacing, its conduction consistently improved during sequential pacing. This improvement of conduction was related to a greater membrane recovery of a portion of the Purkinje fiber, i.e., the portion that was pre-excited by the sequential mode of stimulation. These findings suggest that an important mechanism of the facilitation of conduction observed clinically may be similar; i.e., pre-excitation and consequent earlier recovery from refractoriness of portions of the His-Purkinje system during atrioventricular sequential pacing.     

Effects of manganese chloride, verapamil, and hypoxia on the rate-dependent increase in internal longitudinal resistance of rabbit myocardium

The effects of high rates of stimulation on the internal longitudinal restivity (Ri) and conduction velocity (theta) were studied on rabbit papillary muscle preparations using a silicon-oil chamber. Increasing the rate from 75 to 150/min caused Ri to rise and theta to decrease. The maximum rate of depolarization and action potential duration were also decreased. At a rate of 300/min the effects were more pronounced. Blockade of the slow inward current (Isi) and of the Na-Ca exchange by MnCl2 (5 mmol/L) did not prevent rate-induced changes in these variable. Verapamil (0.02 mmol/L) was also ineffective. Hypoxia (PO2 = 5.3 kPa) at 75/min induced changes in Ri and theta which were similar to those recorded at 150/min under aerobic conditions. The effects of high rates of stimulation were potentiated under hypoxia. From the present results it is suggested that Isi and the Na-Ca exchange are not the main determinants of the rate-induced increase in Ri, which could be determined by other intracellular Ca-release mechanisms or by a decrease in myoplasmic pH.     

猫冠状动脉缺血与再灌注对房室传导的影响

急性下壁心肌梗塞常引起房室传导功能障碍,然而这种障碍与心肌缺血的内在联系并不很清楚,本实验在去植物性神经传出纤维的猫上进行,通过模板匹配方法从Ｈｉｓ束电图检测Ａ,Ｈ,Ｖ波并测量两心房间期（ＡＡ）,心房波与Ｈｉｓ波间期（ＡＨ）,Ｈｉｓ波与心室波间期（ＨＶ）和心房波与心室波间期（ＡＶ）。结果如下：结扎右冠状动脉后,２０只动物的ＡＨ间期１４只出现增加（Ａ组）６只未出现增加（Ｂ组）对Ｂ组进行快速心房起博和     

Atrioventricular conduction with and without AV nodal delay: two pathways to the bundle of His in the rabbit heart

The electrophysiological properties of atrioventricular (AV) nodal dual pathways have traditionally been investigated with premature stimuli delivered with right atrial pacing. However, little is known about the functional characteristics of AV nodal inputs outside of this context. Superfused rabbit triangle of Koch preparations (n = 8) and Langendorff-perfused hearts (n = 10) were paced throughout the triangle of Koch and mapped electrically and optically for activation pattern, electrogram and optical action potential morphologies, stimulation thresholds, and stimulus-His (S-H) intervals. Optical mapping and changes in His electrogram morphology were used to confirm the activation pathway. Pacing stimuli >or=2 mm above the tricuspid valve caused fast-pathway activation of the AV node and His with a threshold of 2.4 +/- 1.6 mA. An area directly below the coronary sinus had high thresholds (8.6 +/- 1.4 mA) that also resulted in fast-pathway excitation (P < 0.001). S-H intervals (81 +/- 19 ms) for fast-pathway activation remained constant throughout the triangle of Koch, reflecting the AV delay. Stimuli applied <2 mm from the tricuspid valve resulted in slow pathway (SP) excitation or direct His excitation (4.4 +/- 2.2 mA threshold; P < 0.001 compared with fast pathway). For SP/His pacing, S-H intervals showed a strong dependence on the distance from the His electrode and were significantly lower than S-H intervals for fast-pathway activation. SP/His pacing also displayed characteristic changes in His electrogram morphology. In conclusion, optical maps and S-H intervals for SP/His activation suggest that AV conduction via SP bypasses the compact AV node via the lower nodal bundle, which may be utilized to achieve long-term ventricular synchronization.     

Colonial conduction systems in the Anthozoa: Octocorallia.

1. The octocorals Alcyonium digitatum, Pennatula phosphorea and Virgularia mirabilis each have a through-conducting nerve net. The nerve net demonstrated electrophysiologically may well be the same as that previously shown by the use of histological techniques. 2. It exhibits both facilitation and defacilitation in the rate of conduction of pulses. 3. The distance of spread of nerve net activity is not limited by the number of stimuli applied. 4. The nerve net controls fast muscle contractions; the frequency of pulses is important in determining which muscles contract and in which sequence. 5. The nerve net is 'spontaneously' active. 6. A previously undescirbed slow system has been identified in Pennatula. It has many of the properties of slow systems in sea anemones and may well be ectodermal. It is suggested that multiple conduction systems are of common occurrence in the Anthozoa.     

On the possible role of focal cooling of the heart in the mechanism of repetitive ventricular extra beats

The role of myocardial foci in the mechanism of ventricular arrhythmias was studied by local cooling of the intact dog heart. At normal heart rate conduction delay in the focus is not sufficient to account for re-entry of impulses. However, a premature stimulus applied near the refractory period caused sudden prolongation of conduction giving rise to nonstimulated extra beats, arising probably as a result of re-entry. The phenomenon is presumably due to the fact that at this time a large portion of the fibres has not yet recovered excitability. With increasing size of the focus, there is increased asynchrony of recovery of excitability and premature stimuli falling later in the cycle are able to produce reentry. A negative correlation exists between cycle length and conduction delay and a positive correlation between cycle length and the coupling interval, i.e. the time interval between a premature stimulus and the first nonstimulated extra beat.     

Frequency- and voltage-dependent effects of disopyramide in canine Purkinje fibers

The voltage- and frequency-dependent blocking actions of disopyramide were assessed in canine Purkinje fibers within the framework of concentrations, membrane potentials, and heart rates which have relevance to the therapeutic actions of this drug. Vmax was used to assess the magnitude of sodium channel block. Disopyramide produced a concentration- and rate-dependent increase in the magnitude and kinetics of Vmax depression. Effects on activation time (used as an estimate of drug effect on conduction) were exactly analogous to effects on Vmax. A concentration-dependent increase in tonic block was also observed. Despite significant increases in tonic block at more depolarized potentials, rate-dependent block increased only marginally with membrane potential over the range of potentials in which propagated action potentials occur. Increases in extracellular potassium concentration accentuated drug effect on Vmax but attenuated drug effect on action potential duration. Recovery from rate-dependent block followed two exponential processes with time constants of 689 +/- 535 ms and 15.7 +/- 2.7 s. The latter component represents dissociation of drug from its binding site and the former probably represents recovery from slow inactivation. A concentration-dependent increase in the amplitude of the first component suggested that disopyramide may promote slow inactivation. There was less than 5% recovery from block during intervals equivalent to clinical diastole. Thus, depression of beats of all degrees of prematurity was similar to that of basic drive beats. Prolongation of action potential duration by therapeutic concentrations of drug following a long quiescent interval was minimal. However, profound lengthening of action potential duration occurred following washout of drug effect at a time when Vmax depression had reverted to normal, suggesting that binding of disopyramide to potassium channels may not be readily reversed. Variable effects on action potential duration may thus be attributed to a block of the window current flowing during the action potential being partially or over balanced by block of potassium channels. Purkinje fiber refractoriness was prolonged in a frequency-dependent manner. Disopyramide did not significantly alter the effective refractory period of basic beats but did increase the effective refractory period of sequential tightly coupled extra stimuli. The results can account for the antiarrhythmic actions of disopyramide during a rapid tachycardia and prevention of its initiation by programmed electrical stimulation.     

The effect of propranolol and dimethylpropranolol on cardiac conduction.

Isolated dog hearts perfused with blood from a donor dogand driven at two heart rates were used to compare the effects of propranolol with those of its quaternary ammonium derivative on atrial, atrioventricular (AV) nodal, and His-Purkinje conduction. Propranolol slowed only AV-nodal conduction, increasing the minimal conduction time and the effect of prematurity, without affecting fatigue. Practolol did not have this effect. Dimethylpropranolol had similar but not identical effects on the AV node, but also slowed atrial and ventricular conduction. In contrast with the quaternary derivative of lidocaine, dimethylpropranolol's effect on atrial and ventricular conduction was not dependent on the heart rate. The effect of dimethylpropranolol on ventricular conduction was observed at doses lower than those reported by others to be antiarrhythmic.     

Electrophysiological effects of ethmozine in perfused rabbit hearts

His-bundle electrocardiography was used to evaluate the effects of ethmozine on cardiac conduction in isolated perfused rabbit hearts electrically driven at cycle lengths of 320 and 250 ms. There was no significant change in conduction until high concentrations of ethmozine were reached. His-Purkinje and atrioventricular (AV) nodal conduction were slowed significantly at 0.1 microgram/mL and atrial conduction at 1.0 microgram/mL. Conduction block occurred at 10.0 micrograms/mL in all the hearts treated. Effects of the drug (0.1 and 0.01 microgram/mL) on conduction of extrasystoles were also studied in hearts driven at a basic cycle length of 270 ms. No significant change was observed in atrial conduction of extrasystoles throughout the coupling intervals tested at both concentrations. Ethmozine (0.01 and 0.1 microgram/mL) caused slowing of His-Purkinje conduction of extrasystoles but the effect of the drug did not change as a function of the coupling interval. An interval-dependent increase in AV-nodal conduction time was observed, with the maximum slowing of conduction occurring at coupling intervals close to the effective refractory period of the AV node. AV-nodal functional refractory period was increased significantly by ethmozine (0.01 and 0.1 microgram/mL). The effective refractory period was significantly increased only at the higher concentration.     

A mathematical model of human atrioventricular nodal function incorporating concealed conduction

This work develops a mathematical model for the atrioventricular (AV) node in the human heart, based on recordings of electrical activity in the atria (the upper chambers of the heart) and the ventricles (the lower chambers of the heart). Intracardiac recordings of the atrial and ventricular activities were recorded from one patient with atrial flutter and one with atrial fibrillation. During these arrhythmias, not all beats in the atria are conducted to the ventricles. Some are blocked (concealed). However, the blocked beats can affect the properties of the AV node. The activation times of the atrial events were regarded as inputs to a mathematical model of conduction in the AV node, including a representation of AV nodal concealment. The model output was compared to the recorded ventricular response to search for and identify the best possible parameter combinations of the model. Good agreement between the distribution of interbeat intervals in the model and data for durations of 5 min was achieved. A model of AV nodal behavior during atrial flutter and atrial fibrillation could potentially help to understand the relative roles of atrial input activity and intrinsic AV nodal properties in determining the ventricular response.     

Correlation of PP and PR intervals in premature low birth weight infants.

We examined the developmental change by which autonomic neural activity associated respiration modulates spontaneous firing rate of sinus (SA) node and atrioventricular (AV) conduction in premature infants born with low birth weight (LBWI). The purpose of this study was to clarify whether variation of PR is correlated with that of PP or those are independent in LBWI with immature autonomic nervous system. We investigated, therefore, whether there are spontaneous functional differences in the innervation of SA and AV nodes. Further, we evaluated the maturation of autonomic nervous system progressing in the period, on the day of birth (Day 0) to approximately one month after the birth (Month 1). This study was performed in thirteen LBWI during deep sleep. EEG, EOG, ECG, respiratory waves were digitized on line, spontaneous firing cycle of SA node (PP), and AV nodal conduction time (PR) that were recorded on Day 0 and Month 1. Then, the data were analyzed as follows: 1) correlations among the means and standard deviations (SD) of PP, PR and RR, 2) variance evaluation of PP and PR intervals by Lorenz plot analysis method, 3) correlation analysis among PP, PR and RR intervals by linear regression method and 4) frequency analysis for PP and PR intervals by high-speed Fourier transform method (FFT) and determination of frequency density. The PP interval decreased as growing in the period. Contrary PR interval increased. In LBWI, the automatic nervous activities including parasympathetic nerve activity for spontaneous firing cycle of SA node and ventricular excitation cycle on Month 1 were higher than Day 0. It was assumed that the vagal nerve activity for the AV conduction was enhanced. However, there was no significant change in linear regression slope for the spontaneous firing cycle of SA node and the AV conduction time. Postnatal LF/HF changes for PP and PR obtained by frequency analysis, were opposite. Therefore, it was suggested that the maturity of autonomic nervous system progresses in the period, Day 0 to approximately Month 1, but the variations in PP and PR are independent each other.     

Respiratory modulation of the autonomic nervous system during Cheyne-Stokes respiration

Cheyne-Stokes respiration (CSR) is associated with increased mortality among patients with heart failure. However, the specific link between CSR and mortality remains unclear. One possibility is that CSR results in excitation of the sympathetic nervous system. This review relates evidence that CSR exerts acute effects on the autonomic nervous system during sleep, and thereby influences a number of cardiovascular phenomena, including heart rate, blood pressure, atrioventricular conduction, and ventricular ectopy. In patients in sinus rhythm, heart rate and blood pressure oscillate during CSR in association with respiratory oscillations, such that both peak heart rate and blood pressure occur during the hyperpneic phase. Inhalation of CO2 abolishes both CSR and the associated oscillations in heart rate and blood pressure. In contrast, O2 inhalation sufficient to eliminate hypoxic dips has no significant effect on CSR, heart rate, or blood pressure. In patients with atrial fibrillation, ventricular rate oscillates in association with CSR despite the absence of within-breath respiratory arrhythmia. The comparison of RR intervals between the apneic and hyperpneic phases of CSR indicates that this breathing disorder exerts its effect on ventricular rate by inducing cyclical changes in atrioventricular node conduction properties. In patients with frequent ventricular premature beats (VPBs), VPBs occur more frequently during the hyperpneic phase than the apneic phase of CSR. VPB frequency is also higher during periods of CSR than during periods of regular breathing, with or without correction of hypoxia. In summary, CSR exerts multiple effects on the cardiovascular system that are likely manifestations of respiratory modulation of autonomic activity. It is speculated that the rhythmic oscillations in autonomic tone brought about by CSR may ultimately contribute to the sympatho-excitation and increased mortality long observed in patients with heart failure and CSR.     

Dual AV Nodal Nonreentrant Tachycardia Resulting in Inappropriate ICD Therapy in a Patient with Cardiac Sarcoidosis

Dual atrioventricular nodal nonreentrant tachycardia (DAVNNT) occurs due to concurrent antegrade conduction over fast and slow atrioventricular nodal pathways and is treated by slow pathway modification. We describe a unique case of a patient with cardiac sarcoidosis who received inappropriate ICD shocks for DAVNNT. Atrial and ventricular device electrograms satisfied both rate and V>A criteria for ventricular tachycardia. We postulate that alterations in refractoriness and conduction as is seen in cardiac sarcoidosis (CS) may have contributed to occurrence of DAVNNT.     

One-Dimensional Mathematical Model of the Atrioventricular Node Including Atrio-Nodal, Nodal, and Nodal-His Cells

Mathematical models are a repository of knowledge as well as research and teaching tools. Although action potential models have been developed for most regions of the heart, there is no model for the atrioventricular node (AVN). We have developed action potential models for single atrio-nodal, nodal, and nodal-His cells. The models have the same action potential shapes and refractoriness as observed in experiments. Using these models, together with models for the sinoatrial node (SAN) and atrial muscle, we have developed a one-dimensional (1D) multicellular model including the SAN and AVN. The multicellular model has slow and fast pathways into the AVN and using it we have analyzed the rich behavior of the AVN. Under normal conditions, action potentials were initiated in the SAN center and then propagated through the atrium and AVN. The relationship between the AVN conduction time and the timing of a premature stimulus (conduction curve) is consistent with experimental data. After premature stimulation, atrioventricular nodal reentry could occur. After slow pathway ablation or block of the L-type Ca²⁺ current, atrioventricular nodal reentry was abolished. During atrial fibrillation, the AVN limited the number of action potentials transmitted to the ventricle. In the absence of SAN pacemaking, the inferior nodal extension acted as the pacemaker. In conclusion, we have developed what we believe is the first detailed mathematical model of the AVN and it shows the typical physiological and pathophysiological characteristics of the tissue. The model can be used as a tool to analyze the complex structure and behavior of the AVN.     

Slow rate during AF improves ventricular performance by reducing sensitivity to cycle length irregularity

Atrial fibrillation (AF) is characterized by short and irregular ventricular cycle lengths (VCL). While the beneficial effects of heart rate slowing (i.e., the prolongation of VCL) in AF are well recognized, little is known about the impact of irregularity. In 10 anesthetized dogs, R-R intervals, left ventricular (LV) pressure, and aortic flow were collected for >500 beats during fast AF and when the average VCL was prolonged to 75%, 100%, and 125% of the intrinsic sinus cycle length by selective atrioventricular (AV) nodal vagal stimulation. We used the ratio of the preceding and prepreceding R-R intervals (RR(p)/RR(pp)) as an index of cycle length irregularity and assessed its effects on the maximum LV power, the minimum of the first derivative of LV pressure, and the time constant of relaxation by using nonlinear fitting with monoexponential functions. During prolongation of VCL, there was a pronounced decrease in curvature with the formation of a plateau, indicating a lesser dependence on RR(p)/RR(pp). We conclude that prolongation of the VCL during AF reduces the sensitivity of the LV performance parameters to irregularity.     

Altered sinus nodal and atrioventricular nodal function in freely moving mice overexpressing the A1 adenosine receptor

To investigate whether altered function of adenosine receptors could contribute to sinus node or atrioventricular (AV) nodal dysfunction in conscious mammals, we studied transgenic (TG) mice with cardiac-specific overexpression of the A1 adenosine receptor (A1AR). A Holter ECG was recorded in seven freely moving littermate pairs of mice during normal activity, exercise (5 min of swimming), and 1 h after exercise. TG mice had lower maximal heart rates (HR) than wild-type (WT) mice (normal activity: 437 +/- 18 vs. 522 +/- 24 beats/min, P < 0.05; exercise: 650 +/- 13 vs. 765 +/- 28 beats/min, P < 0.05; 1 h after exercise: 588 +/- 18 vs. 720 +/- 12 beats/min, P < 0.05; all values are means +/- SE). Mean HR was lower during exercise (589 +/- 16 vs. 698 +/- 34 beats/min, P < 0.05) and after exercise (495 +/- 16 vs. 592 +/- 27 beats/min, P < 0.05). Minimal HR was not different between genotypes. HR variability (SD of RR intervals) was reduced by 30% (P < 0.05) in TG compared with WT mice. Pertussis toxin (n = 4 pairs, 150 microg/kg ip) reversed bradycardia after 48 h. TG mice showed first-degree AV nodal block (PQ interval: 42 +/- 2 vs. 37 +/- 2 ms, P < 0.05), which was diminished but not abolished by pertussis toxin. Isolated Langendorff-perfused TG hearts developed spontaneous atrial arrhythmias (3 of 6 TG mice vs. 0 of 9 WT mice, P < 0.05). In conclusion, A1AR regulate sinus nodal and AV nodal function in the mammalian heart in vivo. Enhanced expression of A1AR causes sinus nodal and AV nodal dysfunction and supraventricular arrhythmias.     

Non-uniform electromyographic activity during fatigue and recovery of the vastus medialis and lateralis muscles

The aim of the study was to investigate EMG signal features during fatigue and recovery at three locations of the vastus medialis and lateralis muscles. Surface EMG signals were detected from 10 healthy male subjects with six 8-electrode arrays located at 10%, 20%, and 30% of the distance from the medial (for vastus medialis) and lateral (vastus lateralis) border of the patella to the anterior superior spine of the pelvic. Subjects performed contractions at 40% and 80% of the maximal force (MVC) until failure to maintain the target force, followed by 20 2-s contractions at the same force levels every minute for 20 min (recovery). Average rectified value, mean power spectral frequency, and muscle fiber conduction velocity were estimated from the EMG signals in 10 epochs from the beginning of the contraction to task failure (time to task failure, mean ± SD, 70.7 ± 25.8 s for 40% MVC; 27.4 ± 16.8 s for 80% MVC) and from the 20 2 s time intervals during recovery. During the fatiguing contraction, the trend over time of EMG average rectified value depended on location for both muscles (P < 0.05). After 20-min recovery, mean frequency and conduction velocity of both muscles were larger than in the beginning of the fatigue task (P < 0.05) (supernormal values). Moreover, the trend over time of mean frequency during recovery was affected by location and conduction velocity values depended on location for both muscles (P < 0.05). The results indicate spatial dependency of EMG variables during fatigue and recovery and thus the necessity of EMG spatial sampling for global muscle assessment.     

Synthesis and biological evaluation of benzopyran analogues bearing class III antiarrhythmic pharmacophores

We have synthesized a series of compounds combining the hydroxy-benzopyran ring of vitamin E with the methylsulfonylaminophenyl group of class III antiarrhythmic drugs, connected through tertiary amine moieties. Evaluation of the antiarrhythmic and antioxidant activity of the new compounds was carried out on isolated rat heart preparations using the non-recirculating Langendorff mode. The new analogues were present, at 10 microM concentration, during ischemia and reperfusion. Selected compounds were further studied by a conventional microelectrode method in order to get insight into their cellular mode of action. The most active compound, N-[4-[2-[[2-(3,4-dihydro-6-hydroxy-2,2,7,8-tetramethyl-2H-1-benzopyran-5-yl)ethyl] methylamine]ethyl]phenyl]methanesulfonamide (19a), reduces premature beats, prolongs QT and QRS intervals during ischemia and reperfusion, and reduces MDA content, leading to a fast recovery of the heart. In addition, it exhibits moderate class III antiarrhythmic action.     

Rate of fatigue during repeated submaximal contractions of human quadriceps muscle.

Our purpose was to determine the effect of eight different combinations of contraction intensity, duration, and rest on the rate of fatigue in vastus lateralis muscle. A single combination consisted of contractions at 30 or 70% maximal voluntary contraction (MVC), held for 3 or 7 s with 3- or 7-s rest intervals. Contractions were repeated until the subject could not hold the force for the requisite duration. At regular intervals during each experiment, a brief MVC, a single twitch, and the response to eight stimulation pulses at 50 Hz were elicited. The rate of fatigue was the rate of decline of MVC calculated from regression analysis. Mean rate of fatigue (n = 8) ranged from 0.3 to 25% MVC/min and was closely related (r = 0.98) to the product of the relative force and the duty cycle. Force from 50 Hz stimulation fell linearly and in parallel with MVC. Twitch force was first potentiated and then fell twice as fast as 50 Hz stimulation and MVC (p less than 0.05). Differentiated twitch contraction and relaxation rates were higher at potentiation and lower at the limit of endurance, compared with control values (p less than 0.05). The maximal electromyogram decreased 25% and the submaximal EMG increased to maximal by the end of the protocol, indicating that the entire motor unit pool had been recruited. The close relation between rate of fatigue and the force x time product probably reflects the off-setting interaction of contraction amplitude, duration, and rest interval. This occurs despite the changes in twitch characteristics and the apparent recruitment of fast fatiguing motor units.     

Mapping of reentrant spontaneous polymorphic ventricular tachycardia in a Scn5a+/- mouse model

Two major mechanisms have been postulated for the arrhythmogenic tendency observed in Brugada Syndrome (BrS): delays in conduction or increased heterogeneities in repolarization. We use a contact mapping system to directly investigate the interacting roles of these two mechanisms in arrhythmogenesis using a genetic murine model for BrS for the first time. Electrograms were obtained from a multielectrode recording array placed against the left ventricle and right ventricle (RV) of spontaneously beating Langendorff-perfused wild type (WT) and Scn5a+/- mouse hearts. Scn5a+/- hearts showed activation waves arriving at the epicardial surface consistent with slowed conduction, which was exacerbated in the presence of flecainide. Lines of conduction block across the RV resulting from premature ventricular beats led to the formation of reentrant circuits and polymorphic ventricular tachycardia. WT hearts showed an inverse relationship between activation times and activation recovery intervals measured at the epicardial surface, which resulted in synchronicity of repolarization times. In contrast, Scn5a+/- hearts, despite having smaller mean activation recovery intervals, demonstrated a greater heterogeneity compared with WT. Isochronal maps showed that their normal activation recovery interval gradients at the epicardial surface were disrupted, leading to heterogeneity in repolarization times. We thus directly demonstrate the initiation of arrhythmia in the RV of Scn5a+/- hearts. This occurs as a result of the combination of repolarization heterogeneities leading to lines of conduction block and unidirectional conduction, with conduction slowing allowing the formation of reentrant circuits. The repolarization heterogeneities may also be responsible for the changing pattern of block, leading to the polymorphic character of the resulting ventricular tachycardia.