Purkinje-muscle Junctions Research Articles

Electrophysiological characterization of a 19-years-old male marathon runner suffering a sudden cardiac death

1 in 50,000 of athletes suffers a cardiac student death (SCD) per year, more of them under 35 years of age. Around 25% of these patients had normal structure, implying that other electrical disorder cause these SCD. Determine the electrophysiological causes of a SCD of a young 19-years-old occurred during a marathon with any heart structural diseases. Pathologic left ventricle (PLV) (n = 1, male, 19-years-old) and control left ventricle (CLV) (n = 1, female, 56-years-old) were perfused and imaged using high resolution optical mapping and Di-4-ANEPPS like a dye. Endocardial and endocardial free wall and his bundle were paced to obtain activation time (AT), repolarization time (RT) and action-potential duration (APD). Purkinje-muscle junctions (PMJs) were determine like activation origins far from the his bundle pacing. Effective refractory period (ERP) was determined using S1S2S3S4 short-coupled pacing. The protocol was repeated after isoplenalie injection [500 nM] like β-adrenergic receptor agonist. His-ventricle activation at high frequency pacing was higher in PLV (143ms) than in control (84ms) and decrease in both at similar levels under ISO (≈60ms). APD gradient increase was observed in PLV near PMJs under ISO (from 3ms/mm to 40ms/mm) and any gradient was observed in the control one. Ectopic episodes were observed in PLV under ISO and 82% of the origins had less that 4 mm of distance with the PMJs. In PLV, the ERP in His-pacing is always lower (320, 260, 250 ms) than endocardial (350, 315, 285 ms) pacing but in CLV, the His-pacing ERP was always higher (320, 260, 240 ms) that endocardial pacing (280, 240, 220 ms). Ventricular fibrillation (VF) was observed in PLV after his bundle pacing at high frequency (more than 330 ms) and any VF was observed in CLV. During this VF, 76% of the focal activities had less than 4 mm of distance with the PMJs. Conduction system (CS) of the PLV shows high sensitivity to high frequency pacing and to presence of ISO. Ectopic episodes and APD gradient near PMJs may show the role of Purkinje network like arrhythmic source. Indeed, the shorter ERP during His-pacing than in the endocardium, give the possibility to produce a macro-re-entry in the conduction system and maintain the arrhythmia with focal activities. CS abnormalities likely played a critical role in arrhythmogenicity and maintenance of VF in this patient during sudden cardiac death.

A case study: High resolution optical mapping of a 19 year old male victim of sudden cardiac death during a marathon

Fifty thousand athletes suffer sudden cardiac death every year due to ventricular fibrillation (VF). Most sudden cardiac deaths of young patients have unexplained origin due to the absence of structural or electrical disease. Purkinje network is essential for a normal heart function, however, its role during electrical pathologies remains unclear. A case study to investigate the electrophysiological properties and the Purkinje network role in a 19 years old male after suffering a fatal sudden cardiac arrest during a marathon event. A coronary-perfused left ventricular preparation was imaged using high resolution optical mapping of epicardial and endocardial surfaces using a voltage-sensitive dye, Di-4-ANEPPS. Activation time, repolarization time and action potential duration were assessed during paced activity through the His bundle and endocardial and epicardial surfaces. Conduction system activation origins were identified as distant endocardial origins during His bundle pacing. Short-coupled S1S2S3S4 pacing was used to determine effective refractory period (ERP). Pacing protocols were repeated in the presence of isoprenaline (ISO) at 100 nM, 500 nM and 1 μM to mimic stress conditions. No changes in total activation time are observed during myocardial pacing cycle lengths of 667ms in control (63ms) and under ISO (up to 64ms). In contrary, His-ventricle delay during conduction system pacing was shorted from 61ms in control to 42ms, 44ms and 16ms under 100 nM, 500 nM and 1 μM of ISO respectively. Under His pacing, local APD gradients are observed near Purkinje-muscle junctions under ISO (from 3ms/mm and 3 ms/mm to 40ms/mm and 41ms/mm). ERP under His pacing was 55ms shorter than endocardial pacing. 82% of the ectopy origins observed have less than 4 mm distance from the PMJs. Repeated focal activations were observed during VF and 76% of them had less than 4 mm distance from PMJs. No structural abnormalities were identified under 9.4 T MRI. Conduction system electrical abnormalities play a role in arrhythmogenicity and maintenance of VF in this patient during sudden cardiac death.

Role of Purkinje-muscle junction in early ventricular fibrillation in a porcine model: Beyond the trigger concept.

The role of the Purkinje network in triggering ventricular fibrillation (VF) has been studied; however, its involvement after onset and in early maintenance of VF is controversial. We studied the role of the Purkinje-muscle junctions (PMJ) on epicardial-endocardial activation gradients during early VF. In a healthy, porcine, beating-heart Langendorff model [control, n = 5; ablation, n = 5], simultaneous epicardial-endocardial dominant frequent mapping was used (224 unipolar electrograms) to calculate activation rate gradients during the onset and early phase of VF. Selective Purkinje ablation was performed using Lugol's solution, followed by VF re-induction and mapping and finally, histological evaluation. Epicardial activation rates were faster than endocardial rates for both onset and early VF. After PMJ ablation, activation rates decreased epicardially and endocardially for both onset and early VF [Epi: 9.7 ± 0.2 to 8.3 ± 0.2 Hz (p <.0001) and 10.9 ± 0.4 to 8.8 ± 0.3 Hz (p < .0001), respectively; Endo: 8.2 ± 0.3 Hz to 7.4 ± 0.2 Hz (p < .0001) and 7.0 ± 0.4 Hz to 6.6 ± 0.3 Hz (p = .0002), respectively]. In controls, epicardial-endocardial activation rate gradients during onset and early VF were 1.7 ± 0.3 Hz and 4.5 ± 0.4 Hz (p < .001), respectively. After endocardial ablation of PMJs, these gradients were reduced to 0.9 ± 0.3 Hz (onset VF, p < .001) and to 2.2 ± 0.3Hz (early VF, p <.001). Endocardial-epicardial Purkinje fiber arborization and selective Purkinje fiber extinction after only endocardial ablation (not with epicardial ablation) was confirmed on histological analysis. Beyond the trigger paradigm, PMJs determine activation rate gradients during onset and during early maintenance of VF.

Pro- and anti-arrhythmic effects of TRPM4 inhibition on ventricular fibrillation trigger and substrate mechanisms

Ventricular Fibrillation (VF) is a major cause of sudden cardiac death. Purkinje fibers (PF) are known to play an important role in triggering and maintaining VF. Previous studies have highlighted the role of TRPM4 channels in repolarization properties of PFs, but their potential impact on arrhythmogenesis and VF dynamics remains unknown. To investigate the role of TRPM4 channels in Purkinje-mediated trigger and substrate mechanisms. Endocardial optical mapping experiments were performed in sheep perfused left ventricular wedge preparations using a high-resolution CMOS camera. Purkinje-Muscle Junctions (PMJ) were localized through PF stimulation and identification of the breakthrough sites. Arrhythmias were induced either by isoprenaline perfusion (ISO; 1 μM; n = 7) or by endocardial burst pacing (10 Hz; n = 6) and their spatiotemporal dynamics quantified with or without 9-Phenanthrol (9PHE; 45 μM), a known TRPM4 inhibitor. ISO perfusion provoked focal tachy-arrhythmias originating from the PFs confirmed by the co-localization of the exit sites with previously identified PMJs. 9PHE reduced the rate of spontaneous focal activity and activation patterns were no longer correlated to the PMJs. However, following burst pacing, inhibition of TRPM4 led to a higher propensity of VF than ventricular tachycardia (VT). For the induced VT episodes, we observed a significant increase of DF (3.7 ± 0.7 Hz vs. 4.8 ± 0.8 Hz) and a significant decrease of regularity index (0.94 ± 0.05 vs. 0.84 ± 0.07) at the PMJs after 9PHE perfusion, while a significant increase in long lasting rotors was observed ( P = 0.044; for rotor number and P = 0.005; for rotor duration). A significant increase in focal activity (15 ± 2 μpixel/ms vs. 30 ± 9 μpixel/ms) was found during VF episodes. These results suggest that TRPM4 inhibition has anti-arrhythmic effects by preventing VF triggers from PFs, while at the same time increasing the complexity of induced ventricular arrhythmias.

Role of the Purkinje-Muscle Junction on the Ventricular Repolarization Heterogeneity in the Healthy and Ischemic Ovine Ventricular Myocardium.

Alteration of action potential duration (APD) heterogeneity contributes to arrhythmogenesis. Purkinje-muscle junctions (PMJs) present differential electrophysiological properties including longer APD. The goal of this study was to determine if Purkinje-related or myocardial focal activation modulates ventricular repolarization differentially in healthy and ischemic myocardium. Simultaneous epicardial (EPI) and endocardial (ENDO) optical mapping was performed on sheep left ventricular (LV) wedges with intact free-running Purkinje network (N = 7). Preparations were paced on either ENDO or EPI surfaces, or the free-running Purkinje fibers (PFs), mimicking normal activation. EPI and ENDO APDs were assessed for each pacing configuration, before and after (7 min) of the onset of no-flow ischemia. Experiments were supported by simulations. In control conditions, maximal APD was found at endocardial PMJ sites. We observed a significant transmural APD gradient for PF pacing with PMJ APD = 347 ± 41 ms and EPI APD = 273 ± 36 ms (p < 0.001). A similar transmural gradient was observed when pacing ENDO (49 ± 31 ms; p = 0.005). However, the gradient was reduced when pacing EPI (37 ± 20 ms; p = 0.005). Global dispersion of repolarization was the most pronounced for EPI pacing. In ischemia, both ENDO and EPI APD were reduced (p = 0.005) and the transmural APD gradient (109 ± 55 ms) was increased when pacing ENDO compared to control condition or when pacing EPI (p < 0.05). APD maxima remained localized at functional PMJs during ischemia. Local repolarization dispersion was significantly higher at the PMJ than at other sites. The results were consistent with simulations. We found that the activation sequence modulates repolarization heterogeneity in the ischemic sheep LV. PMJs remain active following ischemia and exert significant influence on local repolarization patterns.

Role of Purkinje network in maintaining ventricular fibrillation before and after focal catheter ablation of Purkinje fibers in sheep left ventricle

Ventricular Fibrillation (VF) is one of the most frequent causes of sudden cardiac death. It is known that Purkinje fibers (PF) play an important role of arrhythmia trigger and recent studies suggest a potential role of these fibers as a substrate maintaining VF. The goal of this study was to define the role of Purkinje-muscle junctions (PMJ) in maintaining VF and to determine the effect of catheter ablation of these junctions. Optical mapping experiments were performed in coronary-perfused LV wedge preparations from sheep ( n = 8), stained with Di-4-ANBDQBS and using LED illumination at 660 nm. CMOS camera (MiCAM, BrainVision) was used to obtain endocardial recordings. PMJ were localized through PF stimulation and were compared to late activation zones (LAZ). Endocardial burst pacing (10 Hz) was applied to trigger 10 minutes of VF, before and after PMJ ablation (30 W, 15 s), and recordings were acquired every 2 minutes. Phase mapping was used to quantify rotor and focal dynamics. No dominant frequency differences between PMJ and LAZ were found for all VF episodes, before ( P = 0.81) and after ( P = 0.79) PMJ ablation. No change in focal activity was observed during this initial phases of VF. However, a tendency for colocalization for distances between PMJs and rotors was observed before ablation. Distances increased significantly (20 ± 7 mm vs. 24 ± 7 mm; P = 0.009) after ablation. Moreover, a decrease in mean rotor duration and a significant increase in rotor number for all VF episodes (6 ± 4 vs. 12 ± 11; P = 0.026) were also found after ablation. These results suggest that the PMJ is involved in maintaining VF by playing a role in rotor dynamics.

An Optimization-Based Algorithm for the Construction of Cardiac Purkinje Network Models.

This work presents a new algorithm for the construction of a model for the Purkinje network (PN) of the heart. The algorithm is based on a method called constructive constrained optimization (CCO), which was reformulated for the specific case of automatic PN generation. The proposed optimization-based algorithm is referred to as constructive optimization (CO). The CO method iteratively constructs the PN by minimizing the total length of the generated PN tree. In addition, it can take into account some important topological information of the PN, such as the location of the Purkinje-muscle junctions and the average bifurcation angle found in the literature. To validate the model, the new method was compared with the classical L-system method for generating PN models and to a recently proposed image-based technique. The results show that the CO is able to construct PNs with geometric features and activation times that are in good agreement with those reported in the literature and to those obtained by the other aforementioned alternatives.

A coupled 3D–1D numerical monodomain solver for cardiac electrical activation in the myocardium with detailed Purkinje network

We present a model for the electrophysiology in the heart to handle the electrical propagation through the Purkinje system and in the myocardium, with two-way coupling at the Purkinje-muscle junctions. In both the subproblems the monodomain model is considered, whereas at the junctions a resistor element is included that induces an orthodromic propagation delay from the Purkinje network towards the heart muscle. We prove a sufficient condition for convergence of a fixed-point iterative algorithm to the numerical solution of the coupled problem. Numerical comparison of activation patterns is made with two different combinations of models for the coupled Purkinje network/myocardium system, the eikonal/eikonal and the monodomain/monodomain models. Test cases are investigated for both physiological and pathological activation of a model left ventricle. Finally, we prove the reliability of the monodomain/monodomain coupling on a realistic scenario. Our results underlie the importance of using physiologically realistic Purkinje-trees with propagation solved using the monodomain model for simulating cardiac activation.

Simulation Methods and Validation Criteria for Modeling Cardiac Ventricular Electrophysiology.

We describe a sequence of methods to produce a partial differential equation model of the electrical activation of the ventricles. In our framework, we incorporate the anatomy and cardiac microstructure obtained from magnetic resonance imaging and diffusion tensor imaging of a New Zealand White rabbit, the Purkinje structure and the Purkinje-muscle junctions, and an electrophysiologically accurate model of the ventricular myocytes and tissue, which includes transmural and apex-to-base gradients of action potential characteristics. We solve the electrophysiology governing equations using the finite element method and compute both a 6-lead precordial electrocardiogram (ECG) and the activation wavefronts over time. We are particularly concerned with the validation of the various methods used in our model and, in this regard, propose a series of validation criteria that we consider essential. These include producing a physiologically accurate ECG, a correct ventricular activation sequence, and the inducibility of ventricular fibrillation. Among other components, we conclude that a Purkinje geometry with a high density of Purkinje muscle junctions covering the right and left ventricular endocardial surfaces as well as transmural and apex-to-base gradients in action potential characteristics are necessary to produce ECGs and time activation plots that agree with physiological observations.

Influence of the Purkinje-muscle junction on transmural repolarization heterogeneity.

To elucidate the properties of the PMJ and myocardium underlying these effects. Transmural heterogeneity of action potential duration (APD) is known to play an important role in arrhythmogenesis. Regions of non-uniformities of APD gradients often overlap considerably with the location of Purkinje-muscle junctions (PMJs). We therefore hypothesized that such junctions are novel sources of local endocardial and transmural heterogeneity of repolarization, and that remodelling due to heart failure modulates this response. Spatial gradients of endocardial APD in left ventricular wedge preparations from healthy sheep (n = 5) were correlated with locations of PMJs identified through Purkinje stimulation under optical mapping. APD prolongation was dependent on proximity of the PMJ to the imaged surface, whereby shallow PMJs significantly modulated local APD when stimulating either Purkinje (P = 0.0116) or endocardium (P = 0.0123). In addition, we model a PMJ in 5 × 5× 10 mm transmural tissue wedges using healthy and novel failing human ventricular and Purkinje ionic models. Short distances of the PMJ to cut surfaces (<0.875 mm) revealed that APD maxima were localized to the PMJ in healthy myocardium, whereas APD minima were observed in failing myocardium. Amplitudes and spatial gradients of APD were prominent at functional PMJs and quiescent PMJs. Furthermore, increasing the extent of Purkinje fibre branching or decreasing tissue conductivity augmented local APD prolongation in both failing and non-failing models. The Purkinje network has the potential to influence myocardial AP morphology and rate-dependent behaviour, and furthermore to underlie enhanced transmural APD heterogeneities and spatial gradients of APD in non-failing and failing myocardium.

Abstract 19817: Influence of the Purkinje Conduction System on the Ekg: A Modeling Study

Introduction - Computational modeling of cardiac electrophysiology (EP) is important for exploring the mechanisms that underlie fatal arrhythmias. Methods are limited for anatomically mapping the Purkinje conduction system (PCS) in whole hearts, and incorrect definition of the PCS geometry and/or conduction velocity leads to incorrectly modeled activation wavefronts, fractioned QRS, and T-wave inversion. The objective of this study was to design a PCS that resulted in the best simulated six-lead electrocardiogram (ECG), while maintaining consistency with known anatomy. Methods - Diffusion tensor (DT) MRI was used to define gross anatomy and fiber orientations, combined with a cell model to build a finite element model of rabbit cardiac EP, from which the six-lead ECG was simulated. An in vivo six-lead rabbit ECG served as a reference for the computed ECG. The number and distribution of Purkinje-muscle junctions (PMJ) and the conduction velocity in RV, LV, and septal branches were varied. Whole-heart activation wavefronts and the resultant ECG were compared to the normal rabbit ECG. Parameters assessed included activation wavefront timing and QRS/T-wave morphology in a six-lead ECG. Results - Forty combinations of PCS geometry and conduction speed were implemented. Increasing the density (from 34 to 399), uniformly distributing the PMJs, and a PCS with branches for earlier septal activation (3.0m/s) and a faster Purkinje conduction speed in the LV (3.0m/s) compared to the RV (2.1m/s) was necessary to produce the correct activation sequence, eliminate QRS fractionations, and produce the best T-wave morphology. The figure shows the comparison of the ECG output from V3 for three different iterations. Conclusion - The reported Purkinje conduction speed is 0.8-2m/s, but a heterogeneous Purkinje conduction speed distribution combined with a high PMJ density is needed to produce computationally accurate ECGs.

A mathematical model of the Purkinje-Muscle Junctions

This paper is devoted to the construction of a mathematical model of the His-Purkinje tree and the Purkinje-Muscle Junctions (PMJ). A simple numerical scheme is proposed in order to perform some simple numerical experiments.

Purkinje-muscle reentry as a mechanism of polymorphic ventricular arrhythmias in a 3-dimensional model of the ventricles.

Multiple electrode mapping of the ventricles during complex tachyarrhythmias has revealed focal subendocardial activation whose mechanism remains unexplained. We hypothesized that reentry involving the Purkinje-muscle junctions (PMJs) may be a mechanism for such focal excitations. We have constructed an anatomically appropriate computerized 3-dimensional model of the mammalian ventricles that includes the Purkinje conduction system and 214 PMJs distributed throughout the endocardium. Isochronal maps during normal excitation, as well as during right or left bundle branch block, resembled experimental measurements and compared well with isochronal maps of propagation in the human heart. Activity observed at both sides of a PMJ in the model showed that propagation from Purkinje fibers to muscle was slower than in the opposite direction. Under these realistic and normal conditions, the evolution of reentrant activity involving muscle and the Purkinje network was simulated. The reentry pattern was independent of the initiation site. It evolved with drifting epicardial breakthroughs and transformed on the endocardium from focal activity to figure-of-8 reentry. In addition, the ECG amplitude undulated during the evolution, and decrease in the cycle period, apparent wavelength, and propagation velocity were observed. Finally, the reentry was terminated if the Purkinje system was disconnected from the muscle before it reached a relative steady state. The simulation results suggest the following: (1) Epicardial breakthroughs and endocardial focal activity may originate at the PMJs. (2) The ECG amplitude may decrease as the reentry stabilizes and the excitation wavelength decreases. (3) The Purkinje system may have a double role in the evolution of reentry: first, it is essential to the reentry at the initial stage; second, it may lead to the establishment of intramyocardial reentry, at which time the Purkinje system becomes irrelevant.

Interaction of Anesthetics and Catecholamines on Conduction in the Canine His--Purkinje System

The findings in papillary muscles that epinephrine facilitates conduction at Purkinje fiber-muscle junctions and in the endocardium are consistent with older observations that activation of myocardial beta-adrenergic receptors speeds conduction and activation in the heart and thereby increases the synergy of contraction (46,47). The cellular mechanism underlying this action is probably increased cell-to-cell coupling between muscle fibers secondary to elevation of cyclic AMP (19,48). However, the findings that epinephrine alone or with halothane transiently slows conduction in the Purkinje layer while simultaneously improving conduction across Purkinje-muscle junctions and in the endocardium may represent proarrhythmic actions. These actions could facilitate arrhythmogenesis by transiently increasing regional differences of activation and repolarization times in the conduction system and myocardium and thereby increasing vulnerability to induction of reentry by premature impulses. Such a proarrhythmic effect could explain an older observation that low-dose norepinephrine infusions decrease the threshold for induction of fibrillation by two premature beats in pentobarbital-anesthetized animals (49). The cellular basis underlying the different responses of Purkinje fibers and the endocardial muscle layer to catecholamines, in which velocity decreased and increased, respectively, is not known. Our working hypothesis to explain this action in canine Purkinje fibers is a mechanism involving activation of WB4101-sensitive alpha 1-adrenoceptor, G-protein coupling to phospholipase C and the generation of DAG and IP3 leading to modulation of cell-to-cell coupling, which is potentiated in the presence of partial uncoupling by halothane. The different responses of Purkinje and myocardial fibers are speculated to result from differences in the relative density of this subtype of alpha 1-adrenoceptor, differences in the subcellular effector coupling mechanisms, or differences in the specific connexin proteins forming gap junctions between Purkinje and myocardial fibers (50).

Effect of a number of coronary arteries significantly narrowed and status of intraventricular conduction on exercise-induced QRS prolongation in coronary artery disease

Previous studies have shown that myocardial ischemia decreases conduction velocity at Purkinje fibers, Purkinje muscle junctions and ventricular muscle fibers. 1,8 Thus, exercise-induced ischemia in patients with coronary artery disease may produce QRS prolongation. Although the effects of exercise-induced ischemia on the ST-segment changes, myocardial perfusion defects and segmental contraction abnormalities have been extensively studied in patients with coronary artery disease, the effect of exercise-induced ischemia on QRS duration has not been well evaluated. The present study was undertaken to investigate the effect of exercise on QRS duration in patients with coronary artery disease.

Effects of Halothane on Impulse Propagation in Purkinje Fibers and at Purkinje-Muscle Junctions

Alterations in Purkinje-to-muscle conduction may play a role in the development of cardiac arrhythmias. We compared the effects of halothane on impulse propagation in Purkinje fibers with its effects on impulse propagation across the Purkinje-muscle (P-M) junction. In canine Purkinje fibers, halothane (3%) significantly depressed conduction (P less than 0.05). Exposure to halothane altered conduction velocity (theta) in a manner predicted by cable theory; a significant correlation was noted between depression of Vmax and depression of the square of conduction velocity (theta 2) in Purkinje fibers exposed to 3% halothane (n = 11, r = 0.78, P less than 0.01). Halothane (3%) significantly slowed impulse propagation across the P-M junction (P less than 0.05). Vmax and the square of apparent P-M conduction velocity were not significantly correlated (n = 7, r = 0.34, P = 0.45). The data demonstrate that alteration of active membrane properties can account for halothane's slowing of conduction in Purkinje fibers but not for its slowing of conduction across the P-M junction. The data also suggest that a reduction in cell-to-cell coupling may contribute to depression of Purkinje-to-muscle conduction by halothane.

The Purkinje-muscle junction: A determinant of proximal bundle branch action potential duration

The Purkinje-muscle junction: A determinant of proximal bundle branch action potential duration

Electrophysiological evidence of the initiation of arrhythmia by beta-adrenergic blocking agents.

Abstract In 1967 the author (1) mentioned the alternate occurrence of the action potential of the spike type and the one of the spike-and-dome type from the canine Purkinje fibers exposed to a high concentration of magnesium ions. Concurrently Matsuda et al. (2) observed that procaine and low external sodium concentration produced the alternation of the spike type action potentials and the spike-and-dome type from the terminal Purkinje fibers of the dog, which resulted in the partial or complete block of the Purkinje fiber-ventricular muscle conduction. The Purkinje-ventricular delay time is reported also to be increased by hypothermia (2) or low external calcium (3). Sasyniuk and Mendez (4) made it clear that at the Purkinje-muscle junctions the re-entrant beat may emerge as an extra-systole and this event may be facilitated by the electrotonic shortening of action potentials of Purkinje fibers at relatively long distances from the site of conduction block.

Electrophysiological Evidence of the Initiation of Arrhythmia by Beta-Adrenergic Blocking Agents

In 1967 the author (1) mentioned the alternate occurrence of the action potential of the spike type and the one of the spike-and-dome type from the canine Purkinje fibers exposed to a high concentration of magnesium ions. Concurrently Matsuda et al. (2) observed that procaine and low external sodium concentration produced the alternation of the spike type action potentials and the spike-and-dome type from the terminal Purkinje fibers of the dog, which resulted in the partial or complete block of the Purkinje fiber-ventricular muscle conduction. The Purkinje-ventricular delay time is reported also to be increased by hypothermia (2) or low external calcium (3). Sasyniuk and Mendez (4) made it clear that at the Purkinje-muscle junctions the re-entrant beat may emerge as an extra-systole and this event may be facilitated by the electrotonic shortening of action potentials of Purkinje fibers at relatively long distances from the site of conduction block.

A mechanism for reentry in canine ventricualar tissue.

In isolated canine papillary muscle-false tendon preparations it was possible by selecting the pattern of stimulation to obtain conduction block within the peripheral distribution of the Purkinje network. Action potentials recorded just proximal to the site of block were always extremely brief in duration; refractory periods were abbreviated accordingly. When propagation from specialized fibers to muscle fibers was made very critical, conduction block occurred at some Purkinje-muscle junctions while propagation continued through others. Under these conditions very early reentrant activity could be obtained in terminal Purkinje fibers. With proper timing, the impulse propagated back to the false tendon and emerged as a closely coupled extrasystole. Occasionally, the activity returned again to muscle and resulted in a double reentry. Electrotonic shortening of action potentials of Purkinje fibers at relatively long distances upstream from a site of block facilitated the reentry of proximal elements. Partial reentry of the Purkinje system created conditions favoring fractionation of the reentrant wave front.