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Idiopathic verapamil‐sensitive fascicular ventricular tachycardia (VT) is the most common form of Purkinje‐related ventricular tachycardia (PRVT). Left septal fascicle (LSF) involvement and its connections with the other fascicles, have been recently reported as a pathophysiologic mechanism for this form of PRVT. We describe a case of idiopathic PRVT with LSF involvement using omnipolar technology (OT) mapping in relation to a false tendon. Ablation in the area with concealed fusion entrainment did not terminate the tachycardia. However, radiofrequency application in the area of LSF with manifest fusion entrainment, resulted in immediate tachycardia termination. Six months follow‐up showed no tachycardia recurrence. [ABSTRACT FROM AUTHOR]

Introduction: Clinical outcomes of long‐term ventricular septal pacing (VSP) without His‐Purkinje capture remain unknown. This study evaluated the differences in clinical outcomes between conduction system pacing (CSP), VSP, and right ventricular pacing (RVP). Methods: Consecutive patients with bradycardia indicated for pacing from 2016 to 2022 were prospectively followed for the clinical endpoints of heart failure (HF)‐hospitalizations and all‐cause mortality at 2 years. VSP was defined as septal pacing due to unsuccessful CSP implant or successful CSP followed by loss of His‐Purkinje capture within 90 days. Results: Among 1016 patients (age 73.9 ± 11.2 years, 47% female, 48% atrioventricular block), 612 received RVP, 335 received CSP and 69 received VSP. Paced QRS duration was similar between VSP and RVP, but both significantly longer than CSP (p <.05). HF‐hospitalizations occurred in 130 (13%) patients (CSP 7% vs. RVP 16% vs. VSP 13%, p =.001), and all‐cause mortality in 143 (14%) patients (CSP 7% vs. RVP 19% vs. VSP 9%, p <.001). The association of pacing modality with clinical events was limited to those with ventricular pacing (Vp) > 20% (pinteraction <.05). Adjusting for clinical risk factors among patients with Vp > 20%, VSP (adjusted hazard ratio [AHR]: 4.74, 95% confidence interval [CI]: 1.57–14.36) and RVP (AHR: 3.08, 95% CI: 1.44‐6.60) were associated with increased hazard of HF‐hospitalizations, and RVP (2.52, 95% CI: 1.19–5.35) with increased mortality, compared to CSP. Clinical endpoints did not differ between VSP and RVP with Vp > 20%, or amongst groups with Vp < 20%. Conclusion: Conduction system capture is associated with improved clinical outcomes. CSP should be preferred over VSP or RVP during pacing for bradycardia. [ABSTRACT FROM AUTHOR]

The donkey's extraordinary capacity to endure substantial loads over long distances while maintaining equilibrium suggests a distinctive cerebellar architecture specialized in balance regulation. Consequently, our study aims to investigate the intricate histophysiology of the donkey's cerebellum using advanced ultrastructural and immunohistochemical methodologies to comprehend the mechanisms that govern this exceptional ability. This study represents the pioneering investigation to comprehensively describe the ultrastructure and immunohistochemistry within the donkey cerebellum. Five adult donkeys' cerebella were utilized for the study, employing stains such as hematoxylin, eosin, and toluidine blue to facilitate a comprehensive histological examination. For immunohistochemical investigation, synaptophysin (SP), calretinin, and glial fibrillary acidic protein were used and evaluated by the Image J software. Furthermore, a double immunofluorescence staining of SP and neuron‐specific enolase (NSE) was performed to highlight the co‐localization of these markers and explore their potential contribution to synaptic function within the donkey cerebellum. This investigation aims to understand their possible roles in regulating neuronal activity and synaptic connectivity. We observed co‐expression of SP and NSE in the donkey cerebellum, which emphasizes the crucial role of efficient energy utilization for motor coordination and balance, highlighting the interdependence of synaptic function and energy metabolism. The Purkinje cells were situated in the intermediate zone of the cerebellum cortex, known as the Purkinje cell layer. Characteristically, the Purkinje cell's bodies exhibited a distinct pear‐like shape. The cross‐section area of the Purkinje cells was 107.7 ± 0.2 µm2, and the Purkinje cell nucleus was 95.7 ± 0.1 µm2. The length and diameter of the Purkinje cells were 36.4 × 23.4 µm. By scanning electron microscopy, the body of the Purkinje cell looked like a triangular or oval with a meandrous outer surface. The dendrites appeared to have small spines. The Purkinje cells' cytoplasm was rich with mitochondria, rough endoplasmic reticulum, ribosomes, Golgi apparatus, multivesicular bodies, and lysosomes. Purkinje cell dendrites were discovered in the molecular layer, resembling trees. This study sheds light on the anatomical and cellular characteristics underlying the donkey's exceptional balance‐maintaining abilities. Highlights: The donkey's remarkable ability to endure substantial loads over long distances while maintaining equilibrium suggests the presence of a specialized cerebellar architecture dedicated to balance regulation.The objective of this study is to investigate the intricate histophysiology of the donkey's cerebellum using advanced ultrastructural and immunohistochemical methodologies, aiming to comprehend the mechanisms governing this exceptional balancing ability.This study pioneers the comprehensive description of the ultrastructure and immunohistochemistry within the donkey cerebellum, representing a groundbreaking investigation in the field.Five adult donkeys' cerebella were utilized in this study, employing staining techniques such as hematoxylin, eosin, and toluidine blue to facilitate a comprehensive histological examination.Immunohistochemical investigation involved synaptophysin, calretinin, and glial fibrillary acidic protein, evaluated using Image J software, providing valuable insights into their potential roles in regulating neuronal activity and synaptic connectivity.Double immunofluorescence staining of synaptophysin and neuron‐specific enolase highlighted their co‐localization and potential contribution to synaptic function within the donkey cerebellum.Scanning electron microscopy revealed that Purkinje cells had a triangular or oval shape with a meandering outer surface, and the dendrites appeared to have small spines.Transmission electron microscopy showed that the cytoplasm of Purkinje cells contained various organelles, including mitochondria, rough endoplasmic reticulum, ribosomes, Golgi apparatus, multivesicular bodies, and lysosomes.In conclusion, this study sheds light on the anatomical and cellular characteristics underlying the donkey's exceptional balance‐maintaining abilities. [ABSTRACT FROM AUTHOR]

Epicardial adipose tissue (EAT) has been reported to promote myocardial fibrosis and to affect intracardiac conduction. The PR interval reflects the conduction from the atria to the Purkinje fibers and may be associated with the EAT volume, especially in persistent atrial fibrillation (AF) patients. We aimed to investigate the relationship between the EAT and PR interval in patients with persistent AF. We enrolled 268 persistent AF patients who underwent catheter ablation (CA) and divided the patients into two groups: the normal PR interval group (PR interval less than 200 ms: Group N) and long PR interval group (PR interval 200 ms or more: Group L). We then analyzed the association between the total EAT volume around the heart and PR interval and calculated the ratio of the duration of the P wave (PWD) to the PR interval (PWD/PR interval). Moreover, we investigated whether a long PR interval was associated with the outcomes after ablation. The total EAT volume was significantly larger in Group L than Group N (Group N: 131.4 ± 51.8 ml vs. Group L: 151.3 ± 63.3 ml, p = 0.039). A positive correlation was also observed between the PWD/PR interval and EAT volume in Group L (r = 0.345, p = 0.039). A multivariate analysis also revealed that a long PR interval was independently associated with AF recurrence after CA (hazard ratio [HR] 2.071, p = 0.032). The total EAT volume was associated with a long PR interval, and a long PR interval was a significant risk factor for recurrence after ablation in persistent AF patients. [ABSTRACT FROM AUTHOR]

Background: The anatomic extent of the reentry circuit in idiopathic left posterior fascicular ventricular tachycardia (LPF‐VT) is yet to be fully elucidated. We hypothesized that entrainment mapping could be used to delineate the reentry circuit of an LPF‐VT, especially including the upper turnaround point. Methods: Twenty‐three consecutive LPF‐VT patients (mean age, 29 ± 9 years, 18 males) were included. We performed overdrive pacing with entrainment attempts at the left bundle branch (LBB) and the left His bundle (HB) region. Results: Overdrive pacing from the LBB region showed concealed fusion in all 23 patients (post‐pacing interval [PPI], 322.1 ± 64.3 ms; tachycardia cycle length [TCL], 319.0 ± 61.6 ms; PPI‐TCL, 3.1 ± 4.6 ms) with a long stimulus‐to‐QRS interval (287.9 ± 58.0 ms, approximately 90% of the TCL). Pacing from the same LBB region at a slightly faster pacing rate showed manifest fusion with antidromic conduction to the LBB and minimal in‐and‐out time to the LBB potential (PPI‐TCL, 21.3 ± 13.7 ms). Overdrive pacing from the left HB region showed manifest fusion with a long PPI‐TCL (53.9 ± 22.5 ms). Conclusions: Our pacing study results suggest that the upper turnaround point in a reentry circuit of the LPF‐VT may extend to the proximal His‐Purkinje conduction system near the LBB region but below the left HB region. The LPF may constitute the retrograde limb of the reentry circuit. [ABSTRACT FROM AUTHOR]

Myocardial sleeve around human pulmonary veins plays a critical role in the pathomechanism of atrial fibrillation. Besides the well‐known arrhythmogenicity of these veins, there is evidence that myocardial extensions into caval veins and coronary sinus may exhibit similar features. However, studies investigating histologic properties of these structures are limited. We aimed to investigate the immunoreactivity of myocardial sleeves for intermediate filament desmin, which was reported to be more abundant in Purkinje fibers than in ventricular working cardiomyocytes. Sections of 16 human (15 adult and 1 fetal) hearts were investigated. Specimens of atrial and ventricular myocardium, sinoatrial and atrioventricular nodes, pulmonary veins, superior caval vein and coronary sinus were stained with anti‐desmin monoclonal antibody. Intensity of desmin immunoreactivity in different areas was quantified by the ImageJ program. Strong desmin labeling was detected at the pacemaker and conduction system as well as in the myocardial sleeves around pulmonary veins, superior caval vein, and coronary sinus of adult hearts irrespective of sex, age, and medical history. In the fetal heart, prominent desmin labeling was observed at the sinoatrial nodal region and in the myocardial extensions around the superior caval vein. Contrarily, atrial and ventricular working myocardium exhibited low desmin immunoreactivity in both adults and fetuses. These differences were confirmed by immunohistochemical quantitative analysis. In conclusion, this study indicates that desmin is abundant in the conduction system and venous myocardial sleeves of human hearts. [ABSTRACT FROM AUTHOR]

Background: Precise mapping of the Purkinje fiber network is essential in catheter ablation of Purkinje‐related ventricular arrhythmias (PrVAs). We sought to evaluate the mapping ability of a multi‐spline duodecapolar catheter (PentaRay) for PrVAs. Methods: Mappings of Purkinje fibers by PentaRay catheters were compared with those by conventional mapping catheters in consecutive patients undergoing catheter ablation of PrVAs from 2015 to 2022. Results: Sixteen PrVAs (7 premature ventricular contractions or non‐reentrant fascicular tachycardias [PVCs/NRFTs] and 9 fascicular ventricular tachycardias [FVTs]) were retrospectively studied. In PVCs/NRFTs, earliest preceding Purkinje potentials (PPs) could be recorded by the PentaRay catheters but not by the mapping and ablation catheters in 5 cases. At the earliest PP sites, the precedence from the QRS onset was greater, and the amplitude of the preceding potentials was higher in the PentaRay catheter compared with those in the mapping and ablation catheter (−62.0 ± 42.8 vs. −29.4 ± 34.2 ms, P = 0.02; 0.45 ± 0.43 vs. 0.09 ± 0.08 mV, P = 0.02). In FVTs, late diastolic potentials (P1) were recorded by the PentaRay catheters but not by the mapping and ablation catheters or the linear duodecapolar catheter in 2 cases. The amplitude of P1 was higher in the PentaRay catheter compared with that in the linear duodecapolar catheter and the mapping and ablation catheters (0.72 ± 0.49 vs. 0.17 ± 0.18 vs. 0.27 ± 0.21 mV, P = 0.0006, P = 0.002). The localized critical PPs, defined as the earliest preceding potentials in PVCs/NRFTs and P1 in FVTs, could be recorded in all the patients by the PentaRay catheter. The mapping ability of critical PPs of PrVAs was better with the PentaRay catheter than with the conventional mapping catheters (16/16 vs. 9/16, P = 0.004 by McNemar exact test). Conclusions: The PentaRay catheter has clinical advantages in mapping of the Purkinje fiber network to reveal critical PPs as ablation targets of PrVAs. [ABSTRACT FROM AUTHOR]

Introduction: In left bundle branch area pacing (LBBAP), several methods allow determination of lead depth during active fixation inside the septum: among these, visualization of a Purkinje potential indicates that the subendocardial area has been reached. In LBB block (LBBB) patients, fascicular potentials are visible as presystolic only in rare conditions. Methods and Results: Since October 2022 until August 2023, LBBAP was attempted in 21 patients with LBBB at our Center: among the 18 consecutive patients (86%) in which it was successful, focusing on the terminal part of the unipolar ventricular electrogram (VEGM) recorded in the LBBA (where fixation beats occurred and conduction system (CS) capture was confirmed), we always observed discrete high‐frequency, low‐amplitude signals during spontaneous rhythm with LBBB morphology, showing a consistent coupling with the QRS onset, falling in a portion of QRS interval ranging from 58% to 80% of its overall duration, and disappearing during pacing. As found in a recently published case report, these sharp signals could represent the activation of left ventricular CS fibers, occurring passively from the septal working myocardium, and thus appearing lately in the VEGM. Conclusion: The possibility of recognizing discrete high‐frequency, low‐amplitude signals within the terminal portion of the unipolar VEGM, possibly representing left CS potentials, even in patients with LBBB, may constitute a useful additional means to notice operators about having reached the LBBA, thus helping to avoid perforation in the left ventricle. [ABSTRACT FROM AUTHOR]

The inferior olive provides the climbing fibers to Purkinje cells in the cerebellar cortex, where they elicit all-or-none complex spikes and control major forms of plasticity. Given their important role in both short-term and long-term coordination of cerebellum-dependent behaviors, it is paramount to understand the factors that determine the output of olivary neurons. Here, we use mouse models to investigate how the inhibitory and excitatory inputs to the olivary neurons interact with each other, generating spiking patterns of olivary neurons that align with their intrinsic oscillations. Using dual color optogenetic stimulation and whole-cell recordings, we demonstrate how intervals between the inhibitory input from the cerebellar nuclei and excitatory input from the mesodiencephalic junction affect phase and gain of the olivary output at both the sub- and suprathreshold level. When the excitatory input is activated shortly (~50 ms) after the inhibitory input, the phase of the intrinsic oscillations becomes remarkably unstable and the excitatory input can hardly generate any olivary spike. Instead, when the excitatory input is activated one cycle (~150 ms) after the inhibitory input, the excitatory input can optimally drive olivary spiking, riding on top of the first cycle of the subthreshold oscillations that have been powerfully reset by the preceding inhibitory input. Simulations of a large-scale network model of the inferior olive highlight to what extent the synaptic interactions penetrate in the neuropil, generating quasi-oscillatory spiking patterns in large parts of the olivary subnuclei, the size of which also depends on the relative timing of the inhibitory and excitatory inputs. [ABSTRACT FROM AUTHOR]

The existence of "transitional muscular structures" between subendocardial branches (Purkinje fibers) and ventricular working muscle fibers (WF) was first described by the German anatomist, Kurt Goerttler, in 1964. He designated them as "subendocardial nucleus organs." He supposed such fibers functioned as mechanoreceptors, controlling of the intensity of contraction of the ventricular musculature. Brazilian anatomist Ferraz de Carvalho described similar structures in 1993. A thorough literature search failed to identify any other research articles confirming or denying their existence. The objective of this work was to find such structures in subendocardial ventricular walls in human hearts. We collected fifteen formalin-preserved hearts from the Anatomy Department of São Paulo University and sectioned the apical portions on the right and left ventricles according to method used by Goerttler. We utilized conventional histology (light microscopy-LM), scanning electron microscopy (SEM), and a new preservation method called microplastination (MP). At the anterior wall of the right ventricle in the subendocardial region between the interventricular septum and moderator band, we found several bundles of fusiform and helicoidal fibers of similar histology to the WF. The bundles measured between 400 and 1150 µm in length and were separated from adjacent muscular fibers by thin collagen fiber, thus acting as a "pseudo capsule." Some structures seemed to be linked to PF and were appeared to be lymphatic and blood vessels and nerves. We called those structures "cardiac corpuscles" (CC). The observation of the previously "unknown" CC in this initial study confirmed the previous descriptions and its discovery may contribute to new perspectives in the study of cardiac muscle structure and function. [ABSTRACT FROM AUTHOR]

The efficacy of cardiac resynchronization therapy (CRT) in heart failure patients with left bundle branch block (LBBB) is well established with Class I or IIa recommendation according to 2021 ESC Guidelines on cardiac pacing and CRT, whereas non‐LBBB morphology is less recommended. There is insufficient evidence that proves patients with NICD could benefit from CRT. As patients with NICD are characterized by heterogeneity, the effect of CRT on these patients is still controversial. Although the proportion of NICD in the population is lower than that of LBBB patients, it is still worth investigating the effects of CRT on patients with NICD in an era of His‐Purkinje conduction system pacing (HPCSP). [ABSTRACT FROM AUTHOR]

The cerebellum is involved in learning of fine motor skills, yet whether presynaptic plasticity contributes to such learning remains elusive. Here, we report that the EPAC-PKCε module has a critical role in a presynaptic form of long-term potentiation in the cerebellum and motor behavior in mice. Presynaptic cAMP−EPAC−PKCε signaling cascade induces a previously unidentified threonine phosphorylation of RIM1α, and thereby initiates the assembly of the Rab3A−RIM1α− Munc13-1 tripartite complex that facilitates docking and release of synaptic vesicles. Granule cell-specific blocking of EPAC−PKCε signaling abolishes presynaptic long-term potentiation at the parallel fiber to Purkinje cell synapses and impairs basic performance and learning of cerebellar motor behavior. These results unveil a functional relevance of presynaptic plasticity that is regulated through a novel signaling cascade, thereby enriching the spectrum of cerebellar learning mechanisms. [ABSTRACT FROM AUTHOR]

The article focuses on investigating the mechanism behind varying HV intervals observed during wide QRS tachycardia in a 32-year-old female. Topics include the identification of pathway-to-pathway atrioventricular re-entry tachycardia involving right and left free wall pathways, the role of retrograde conduction via a left lateral accessory pathway, and the implications of these findings for electrophysiological study and ablation therapy in managing recurrent palpitations and arrhythmias.

Introduction: Conduction system pacing (CSP), in the form of His bundle pacing (HBP) or left bundle branch pacing (LBBP), is emerging as a valuable cardiac resynchronization therapy (CRT) delivery method. However, patient selection and therapy personalization for CSP delivery remain poorly characterized. We aim to compare pacing‐induced electrical synchrony during CRT, HBP, LBBP, HBP with left ventricular (LV) epicardial lead (His‐optimized CRT [HOT‐CRT]), and LBBP with LV epicardial lead (LBBP‐optimized CRT [LOT‐CRT]) in patients with different conduction disease presentations using computational modeling. Methods: We simulated ventricular activation on 24 four‐chamber heart geometries, including His–Purkinje systems with proximal left bundle branch block (LBBB). We simulated septal scar, LV lateral wall scar, and mild and severe myocardium and LV His–Purkinje system conduction disease by decreasing the conduction velocity (CV) down to 70% and 35% of the healthy CV. Electrical synchrony was measured by the shortest interval to activate 90% of the ventricles (90% of biventricular activation time [BIVAT‐90]). Results: Severe LV His–Purkinje conduction disease favored CRT (BIVAT‐90: HBP 101.5 ± 7.8 ms vs. CRT 93.0 ± 8.9 ms, p <.05), with additional electrical synchrony induced by HOT‐CRT (87.6 ± 6.7 ms, p <.05) and LOT‐CRT (73.9 ± 7.6 ms, p <.05). Patients with slow myocardium CV benefit more from CSP compared to CRT (BIVAT‐90: CRT 134.5 ± 24.1 ms; HBP 97.1 ± 9.9 ms, p <.01; LBBP: 101.5 ± 10.7 ms, p <.01). Septal but not lateral wall scar made CSP ineffective, while CRT was able to resynchronize the ventricles in the presence of septal scar (BIVAT‐90: baseline 119.1 ± 10.8 ms vs. CRT 85.1 ± 14.9 ms, p <.01). Conclusion: Severe LV His–Purkinje conduction disease attenuates the benefits of CSP, with additional improvements achieved with HOT‐CRT and LOT‐CRT. Septal but not lateral wall scars make CSP ineffective. [ABSTRACT FROM AUTHOR]

Introduction: Idiopathic ventricular fibrillation (IVF) is mainly associated with and triggered by short‐coupled (R‐on‐T) ventricular ectopics. However, little is known about the risk of VF associated with long‐coupled premature ventricular complexes (LCPVCs). Objective: To examine the prevalence and characteristics of IVF patients presenting with LCPVCs. Methods: Consecutive patients with IVF and PVCs from five arrhythmia referral centers were reviewed. We included patients presenting LCPVCs, defined as PVCs falling after the end of the T wave, with a normal QTc interval. We evaluated demographics, medical history, and clinical circumstances associated with PVCs and VF episodes. The origin of PVCs was determined by invasive mapping. Results: Seventy‐nine patients with IVF were reviewed. Among them, 12 (15.2%) met the inclusion criteria (8 women, age 36 ± 14 years). Eleven patients had documented LCPVCs initiating repetitive PVCs or sustained VF, whereas 1 had only documented isolated PVCs. In 10 of 12 patients, PVCs were recorded showing both long and short coupling intervals of 418 ± 46 and 304 ± 33 ms, respectively. Mapping showed that PVCs originated from the left Purkinje in 10 patients, from the right Purkinje in 1 patient, and both in 1 patient. Compared to other patients from the initial cohort, IVF with LCPVCs was associated with a left‐sided origin of PVCs (92% in long‐coupled IVF vs. 46% of left Purkinje PVCs in short‐coupled IVF, p =.004). Conclusion: Long‐coupled fascicular PVCs, traditionally recognized as benign, can be associated with IVF in a subset of patients. They can induce IVF by themselves or in association with short‐coupled PVCs. [ABSTRACT FROM AUTHOR]

Introduction: The anatomical substrate for idiopathic left ventricular tachycardia (ILVT) remains speculative. Purkinje networks surrounding false tendons (FTs) might be involved in the reentrant circuit of ILVT. The objective was to evaluate the anatomical and electrophysiological features of false tendons FTs in relation to ILVT. Methods: Intracardiac echocardiography (ICE) was conducted on patients with ILVT. The relationship of the FTs with ILVT was determined using electro‐anatomical mapping. Results: Electrophysiological evaluation and radiofrequency ablation were conducted in 23 consecutive patients with ILVT. FTs were identified in 19/23 cases (82.6%) with P1 potentials during VT recorded at the FT in 14 of these patients (73.7%). Three FT types were identified. In type 1, the FT attached the septum to the base of the posteromedial papillary muscle (PPM) (4/19); type 2 FTs ran between the septum and the PPM apex (3/19), while in type 3, the connection occurred between the septum and apex (11/19) or between the septum and the LV free wall (1/19). The effective ILVT ablation sites were situated at the FT‐PPM (3/19) and the FT‐septum (16/19) attachment sites. Conclusions: This series demonstrates the association between Purkinje fibers and FTs during catheter ablation of ILVT and verifies that left ventricular FTs are an important substrate in this type of tachycardia. [ABSTRACT FROM AUTHOR]

Background: The Purkinje fibers convey the electrical impulses at much higher speed than the working myocardial cells. Thus, the distribution of the Purkinje network is of paramount importance for the timing and coordination of ventricular activation. The Purkinje fibers are found in the subendocardium of all species of mammals, but some mammals also possess an intramural Purkinje fiber network that provides for relatively instantaneous, burst‐like activation of the entire ventricular wall, and gives rise to an rS configuration in lead II of the ECG. Aim: To relate the topography of the horse heart and the distribution and histology of the conduction system to the pattern of ventricular activation as a mechanism for the unique electrical axis of the equine heart. Methods: The morphology and distribution of the cardiac conduction system was determined by histochemistry. The electrical activity was measured using ECG in the Einthoven and orthogonal configuration. Results: The long axis of the equine heart is close to vertical. Outside the nodal regions the conduction system consisted of Purkinje fibers connected by connexin 43 and long, slender parallel running transitional cells. The Purkinje fiber network extended deep into the ventricular walls. ECGs recorded in an orthogonal configuration revealed a mean electrical axis pointing in a cranial‐to‐left direction indicating ventricular activation in an apex‐to‐base direction. Conclusion: The direction of the mean electrical axis in the equine heart is determined by the architecture of the intramural Purkinje network, rather than being a reflection of ventricular mass. [ABSTRACT FROM AUTHOR]

The mammalian cardiac conduction system (CCS) is a multifaceted continuum of electrically distinct, interconnected constructs within the myocardial mass. The key components are the sinus node (SAN), the atrioventricular node (AVN), the His bundle (HB), and the Purkinje fiber network (PF), the latter serendipitously discovered by Jan Evangelista Purkinje in 1839 in the sheep ventricle. In 1893, Wilhelm His, Jr. described a ventricular muscular tract conveying SAN-generated action potentials from the AVN (discovered by Sunao Tawara and Karl Albert Aschoff in 1906) to the PF. In 1906, Keith and Flack completed these explorations by localizing the SAN, the primum movens of CCS, which functions as a biologic oscillator emitting cadenced impulses that travel via the Bachmann bundle to the atrial myocytes and, via internodal pathways, to the AVN. Here these impulses are briefly delayed, enabling atrial systole before continuing via the AVN and the high-speed His-Purkinje conduction axis to signal ventricular contraction. The CCS canonical discoverers (Keith and Flack, Aschoff and Tawara, His, and Purkinje), historical controversies, fundamental notions of anatomy, physiology, and pathology, and therapeutic interventions pertaining to the CCS are the main themes of this review. Any scientist mentioned or unmentioned in this report who contributed directly or indirectly, with correct or inaccurate hypotheses, to the characterization of the CCS deserves our deepest gratitude for the long and painstaking hours spent microscopically scrutinizing heart specimens from multiple mammalian species, including humans. NEW & NOTEWORTHY This report presents the first comprehensive summary of the factors enabling the discovery of the cardiac conduction system (CCS). Biographical highlights and achievements of the CCS canonical discoverers, hypotheses concerning mechanisms underlying sinus node (SAN) automaticity, use of eponyms to denominate a discovery, famous controversies, possible reproachable behavior (e.g., intellectual support for eugenics in post-World War I Germany) by two of the discoverers, and examples of historical mentor-pupil relationships are discussed. [ABSTRACT FROM AUTHOR]

Ever since they were first observed in Purkinje fibers of the heart, funny channels have had close connections to potassium channels. Indeed, funny channels were initially thought to produce a potassium current in the heart called IK2. However, funny channels are completely unlike potassium channels in ways that make their contributions to the physiology of cells unique. An important difference is the greater ability for sodium to permeate funny channels. Although it does not flow through the funny channel as easily as does potassium, sodium does permeate well enough to allow for depolarization of cells following a strong hyperpolarization. This is critical for the function of funny channels in places like the heart and brain. Computational analyses using recent structures of the funny channels have provided a possible mechanism for their unusual permeation properties. [ABSTRACT FROM AUTHOR]

Aim: The goal of this study is to compare fuzzy based purkinje fiber cell(PFC) synchronization and coordination categorization using potassium(K+) channel parameters with K Nearest Neighbor (KNN) and Artificial Neural Network (ANN). Materials and Methods: The PFC Aslanidi model(AM) is used to classify cardiac arrhythmias of K+ channel at different malfunction conditions. In AM, the K+ channel dynamics are well described based on the PFC dataset. ANN and KNN classifiers are used to classify the different PFC classification. Sample size was calculated by keeping threshold 0.05, G Power 80%, confidence interval 95% and enrolment ratio as 1. 20 samples are taken for each analysis to predict the accuracy of the Novel ANN and KNN classifier. Finally, using the Statistical Package for the Social Science (SPSS) programme, the collected dataset(resultant accuracy) can be calculated. Result: PFC normal Action Potential (AP) having AP Duration (APD) is 290ms and Total Cycle Length (TCL) is 1000ms at K+ extracellular levels as 5.4mM. Whereas in abnormal AP indicates APD is 280ms and TCL is 900ms at K+ extracellular levels as 10.4mM. A 10% decrease in APD with normal PFC AP and 10% drop in TCL is responsible for Tachycardia (fast heartbeat), Then PFC data(Normal, Tachycardia, Bradycardia) are sent into the Novel ANN and KNN classifier algorithms. Using SPSS software, the results reveal that ANN accuracy is higher than KNN. Group 1 KNN has a mean of 63.410, a standard deviation of 4.3533, and a standard error mean of .9734, whereas group 2 ANN has a mean of 66.055, a standard deviation of 1.0329, and a standard error mean of .2310. Conclusion: Therefore the changes in PFC K+ channel leads to Hypokalemia which results in cardiac arrhythmia of resting membrane potential and the duration of both the action potential, to a higher extent than the normal. The paper concludes that the ANN classifier predicts better classification in identifying the accuracy of potassium channel parameters when compared to the KNN classifier of PFC synchronization and coordination. [ABSTRACT FROM AUTHOR]

The anisotropic electrical nature of the cardiac tissue, dependent on the fiber orientations and corresponding conductivity tensor components, plays an important role in computational simulations of the electrophysiology of the heart. To date, no accurate technique is utilized to assess how these variations in fiber angles and conductivity change the electrical behavior of the heart. Herein, we make use of six-lead electrocardiograms to demonstrate how this variability affect electrical responses of the heart. To generate an electrocardiogram, consistent with the clinical outputs, the simulation of the Purkinje fibers is also crucial. Moreover, an action potential duration heterogeneity exists among different cells based on their position in the ventricles. In this regard, we simulate a transmural distribution for the action potential duration where the longest repolarization time belongs to the midmyocardial cells. It is demonstrated that variations in fiber angles, from the endocardium to the epicardium, have no significant effect not only on the computational results but also on the clinical response of the electrocardiograms. We also show that different conduction velocities have major effects on the six leads. All together, our results demonstrate that different bounds of fiber angles do not play an important role in electrical cardiac models; however, conduction velocities should be measured and taken into account precisely due to their significant electrophysiological effects. [ABSTRACT FROM AUTHOR]

The article presents the discussion on short or long‐coupled idiopathic ventricular fibrillation. Topics include arrhythmias originated from the left posterior fascicle, the left anterior fascicle and presumably the right ventricular moderator band; and performing with the high suspicion where syncope being related to aborted malignant tachyarrhythmias.

Background: 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. Aim: We studied the role of the Purkinje‒muscle junctions (PMJ) on epicardial–endocardial activation gradients during early VF. Methods: 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. Results: 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 ± 0.3 Hz (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. Conclusions: Beyond the trigger paradigm, PMJs determine activation rate gradients during onset and during early maintenance of VF. [ABSTRACT FROM AUTHOR]

Background: His‐Purkinje conduction system pacing (HPCSP) has been proposed as an alternative to Cardiac Resynchronization Therapy (CRT); however, predictors of echocardiographic response have not been described in this population. Septal flash (SF), a fast contraction and relaxation of the septum, is a marker of intraventricular dyssynchrony. Methods: The study aimed to analyze whether HPCSP corrects SF in patients with CRT indication, and if correction of SF predicts echocardiographic response. This retrospective analysis of prospectively collected data included 30 patients. Left ventricular ejection fraction (LVEF) was measured with echocardiography at baseline and at 6‐month follow‐up. Echocardiographic response was defined as increase in five points in LVEF. Results: HPCSP shortened QRS duration by 48 ± 21 ms and SF was significantly decreased (baseline 3.6 ± 2.2 mm vs. HPCSP 1.5 ± 1.5 mm p <.0001). At 6‐month follow‐up, mean LVEF improvement was 8.6% ± 8.7% and 64% of patients were responders. There was a significant correlation between SF correction and increased LVEF (r =.61, p =.004). A correction of ≥1.5 mm (baseline SF – paced SF) had a sensitivity of 81% and 80% specificity to predict echocardiographic response (area under the curve 0.856, p =.019). Conclusion: HPCSP improves intraventricular dyssynchrony and results in 64% echocardiographic responders at 6‐month follow‐up. Dyssynchrony improvement with SF correction may predict echocardiographic response at 6‐month follow‐up. [ABSTRACT FROM AUTHOR]

Background: His‐Purkinje conduction system pacing (HPCSP) has emerged as an effective alternative to overcome the limitations of right ventricular pacing (RVP) via physiological left ventricular activation, but there remains a paucity of comparative information for His bundle pacing (HBP) and left bundle branch pacing (LBBP). Methods: A Bayesian random‐effects network analysis was conducted to compare the relative effects of HBP, LBBP, and RVP in patients with bradycardia and conduction disorders. PubMed, Embase, Cochrane Library, and Web of Science were systematically searched from database inception until September 21, 2021. Results: Twenty‐eight studies involving 4160 patients were included in this meta‐analysis. LBBP significantly improved success rate, pacing threshold, pacing impedance, and R‐wave amplitude compared with HBP. LBBP also demonstrated a nonsignificant trend towards superior outcomes of lead complications, heart failure hospitalization, atrial fibrillation, and all‐cause death. However, HBP was associated with significantly shorter paced QRS duration relative to LBBP. Despite higher success rates, shorter procedure/fluoroscopy duration, and fewer lead complications, patients receiving RVP were more likely to experience reduced left ventricular ejection fraction, longer paced QRS duration, and higher rates of heart failure hospitalization than those receiving HPCSP. No statistical differences were observed in the remaining outcome measures. Conclusions: This network meta‐analysis demonstrates the efficacy and safety of HPCSP for the treatment of bradycardia and conduction disorders, with differences in pacing parameters, electrophysiology characteristics, and clinical outcomes between HBP and LBBP. Larger‐scale, long‐term comparative studies are warranted for further verification. [ABSTRACT FROM AUTHOR]

Introduction: Ventricular fibrillation (VF) is the main mechanism of sudden cardiac death in patients with hypertrophic cardiomyopathy (HCM). The origin of VF and the success of catheter ablation to eliminate recurrent episodes in this population are poorly understood. Methods and Results: From 2010 to 2014, five patients with HCM (age 21 ± 9 years, three female) underwent invasive electrophysiological studies and ablation at our center after resuscitation from recurrent (9 ± 7) episodes of VF. Ventricular premature beats (VPBs), seen to initiate VF in certain cases, were recorded noninvasively before the ablation procedure. Postprocedural computed tomography (CT) was performed to correlate ablation sites with myocardial hypertrophy in three patients. Outcomes were assessed by clinical follow‐up and implantable cardioverter‐defibrillator interrogations. VPB triggers were localized invasively to the distal left Purkinje conduction system (left posterior fascicle [2], left anterior fascicle [1], and both fascicles [2]). All targeted VF triggers were successfully eliminated by radiofrequency ablation in the left ventricle. Among patients with postablation CT imaging, 93 ± 12% of ablation sites corresponded to hypertrophied segments. Over 50 ± 38 months, four of five patients were free from primary VF without antiarrhythmic drug therapy. One patient who had 13 episodes of VF before ablation had a single recurrence. Conclusion: In our study of patients with HCM and recurrent VF, VF was not initiated from the myocardium but rather from Purkinje arborization. These sources colocalized with the hypertrophic substrate, suggesting electromechanical interaction. Focal ablation at these sites was associated with a marked reduction in VF burden. [ABSTRACT FROM AUTHOR]

The cardiac conduction system is a network of heterogeneous cell population that initiates and propagates electric excitations in the myocardium. Purkinje fibers, a network of specialized myocardial cells, comprise the distal end of the conduction system in the ventricles. The developmental origins of Purkinje fibers and their roles during cardiac physiology and arrhythmia have been reported. However, it is not clear if they play a role during ischemic injury and heart regeneration. Here we introduce a novel tamoxifen-inducible Cre allele that specifically labels a broad range of components in the cardiac conduction system while excludes other cardiac cell types and vital organs. Using this new allele, we investigated the cellular and molecular response of Purkinje fibers to myocardial injury. In a neonatal mouse myocardial infarction model, we observed significant increase in Purkinje cell number in regenerating myocardium. RNA-Seq analysis using laser-captured Purkinje fibers showed a unique transcriptomic response to myocardial infarction. Our finds suggest a novel role of cardiac Purkinje fibers in heart injury. [Display omitted] • A novel inducible Cre strain with specific activity in cardiac conduction system. • Cardiac Purkinje fibers respond to myocardial injury. • Cardiomyocytes may contribute to Purkinje fiber expansion post injury. [ABSTRACT FROM AUTHOR]

The author reflects on the growing use of His-purkinje conduction system pacing (HPCSP) in patients with atrial fibrillation (AF) and heart failure (HF). Also cited are the types of HPCSP like His bundle pacing (HBP) and left bundle branch pacing (LBBP), the feasibility and efficacy of HPCSP in patients with AF and atrioventricular node (AVN) ablation, and the effects of AF on electrical synchrony of HPCSP and BVP.

Omecamtiv mecarbil (OM) is a myosin activator (myotrope), developed as a potential therapeutic agent for heart failure with reduced ejection fraction. To characterize the potential pro‐arrhythmic risk of this novel sarcomere activator, we evaluated OM in a series of International Conference on Harmonization S7B core and follow‐up assays, including an in silico action potential (AP) model. OM was tested in: (i) hERG, Nav1.5 peak, and Cav1.2 channel assays; (ii) in silico computation in a human ventricular AP (hVAP) population model; (iii) AP recordings in canine cardiac Purkinje fibers (PF); and (iv) electrocardiography analysis in isolated rabbit hearts (IRHs). OM had low potency in the hERG (half‐maximal inhibitory concentration [IC50] = 125.5 µM) and Nav1.5 and Cav1.2 assays (IC50 > 300 µM). These potency values were used as inputs to investigate the occurrence of repolarization abnormalities (biomarkers of pro‐arrhythmia) in an hVAP model over a wide range of OM concentrations. The outcome of hVAP analysis indicated low pro‐arrhythmia risk at OM concentration up to 30 µM (100‐fold the effective free therapeutic plasma concentration). In the isolated canine PF assay, OM shortened AP duration (APD)60 and APD90 significantly from 3 to 30 µM. In perfused IRH, ventricular repolarization (corrected QT and corrected JT intervals) was decreased significantly at greater than or equal to 1 µM OM. In summary, the comprehensive proarrhythmic assessment in human and non‐rodent cardiac models provided data indicative that OM did not delay ventricular repolarization at therapeutic relevant concentrations, consistent with clinical findings. [ABSTRACT FROM AUTHOR]

This commentary highlights a "cerebellar classic" by Heinrich Obersteiner (1847–1922), the founder of Vienna's Neurological Institute. Obersteiner had a long-standing interest in the cerebellar cortex, its development, and pathology, having provided one of the early accurate descriptions of the external germinal layer (sometimes called the "marginal zone of Obersteiner" or "Obersteiner layer"). In his communication before the 81st meeting of the Society of German Natural Scientists and Physicians in Salzburg in September 1909, Obersteiner placed special emphasis on the histophysiology of the granule cell layer of the cerebellum and covered most of the fundamental elements of the cerebellar circuitry, on the basis of Ramón y Cajal's neuronism. Those elements are discussed in a historic and a modern perspective, including some recent ideas about the role of granule cells, beyond the mere relay of sensorimotor information from mossy fibers to the Purkinje cells, in learning and cognition. [ABSTRACT FROM AUTHOR]

• Analysis of smooth pursuit eye movements suggests 4 principles of operation of the cerebellar learning circuit. • Climbing fibers cause fast, early, poorly-retained learning at the parallel fiber to Purkinje cell synapse. • Learning transfers to a slow, late, well-retained site in the cerebellar nucleus, guided by Purkinje cells. • A recurrent circuit from Purkinje cells to the inferior olive limits the magnitude of learning in the cerebellar cortex. • The signals that are subjected to plasticity are different in the cerebellar cortex versus the cerebellar nuclei. As a tribute to Masao Ito, we propose a model of cerebellar learning that incorporates and extends his original model. We suggest four principles that align well with conclusions from multiple cerebellar learning systems. (1) Climbing fiber inputs to the cerebellum drive early, fast, poorly-retained learning in the parallel fiber to Purkinje cell synapse. (2) Learned Purkinje cell outputs drive late, slow, well-retained learning in non-Purkinje cell inputs to neurons in the cerebellar nucleus, transferring learning from the cortex to the nucleus. (3) Recurrent feedback from Purkinje cells to the inferior olive, through interneurons in the cerebellar nucleus, limits the magnitude of fast, early learning in the cerebellar cortex. (4) Functionally different inputs are subjected to plasticity in the cerebellar cortex versus the cerebellar nucleus. A computational neural circuit model that is based on these principles mimics a large amount of neural and behavioral data obtained from the smooth pursuit eye movements of monkeys. [ABSTRACT FROM AUTHOR]

Background: Captopril, an angiotensin-converting enzyme inhibitor, and losartan, an angiotensin II receptor blocker, are used for the treatment of hypertension, but their effects on cardiac stereology are unknown. This study, therefore, aimed to examine their effects on cardiac stereology in rats with renovascular hypertension. Methods: This study was conducted at Histomorphometry and Stereology Research Centre, and Cardiovascular Pharmacology Research Lab, Department of Pharmacology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran, in August 2015 to August 2016. Forty-eight rats were allocated to six groups (n=8 per each group): a sham group, which received a vehicle (distilled water) and five renal artery-clipped groups, which received the vehicle, captopril (50 or 100 mg/ kg/day), or losartan (25 or 50 mg/kg/day). After four weeks, the animals' systolic blood pressures (mm Hg) were measured, and the total volumes of their heart, myocardium, endocardium, matrix, and myocardial vessels (mm3), as well as the number of their cardiomyocytes, and Purkinje fibers were determined. Data were analyzed using one-way analysis of variance (ANOVA) followed by least significant difference (LSD) test. P value of equal to or less than 0.05 was considered significant. Results: The renal artery-clipped rats receiving the vehicle had a significantly higher systolic blood pressure (P<0.001); heart weight (g) (P<0.001); and total volume of the heart (P<0.001), myocardium (P=0.020), endocardium (P=0.009), and myocardial vessels (P=0.008); as well as a significantly lower number of cardiomyocytes (P=0.010) and Purkinje cells (P=0.005), than did the rats in the sham group. The renal artery-clipped rats receiving captopril or losartan had a significantly lower systolic blood pressure (P<0.001), heart weight (P=0.007), and total volume of the heart (P<0.001), myocardium (P<0.001), endocardium (P=0.027), and myocardial vessels (P=0.004) than did the renal artery-clipped rats receiving the vehicle. Neither captopril nor losartan prevented a reduction in the number of Purkinje cells, but captopril at the higher dose attenuated cardiomyocyte loss (P=0.010). Conclusion: Captopril and losartan lowered the systolic blood pressure and cardiac hypertrophy but failed to prevent Purkinje cell loss. Captopril only at the higher dose prevented cardiomyocyte loss. Captopril exerted a greater inhibitory effect on cardiac stereology, which warrants further research. [ABSTRACT FROM AUTHOR]

Introduction: Histological studies reported that the His bundle (HB) is partitioned into narrow cords by collagen running in its long axis, providing the anatomical setting necessary for its longitudinal dissociation. Further confirmations came from the demonstration that direct HB pacing normalizes the QRS axis and duration in subjects with proximal HB lesions causing bundle branch block. However, there is no evidence of the possibility of selective HB partitions pacing destined to the composition of branches and fascicles. Methods and Results: We describe a case of intra‐Hisian left bundle branch block in which permanent distal HB pacing corrects left ventricular delay and produces different QRS morphology at different voltage outputs, as an expression of different selective HB compartments recruitment. Conclusion: This case would strengthen the limited data in the literature about HB longitudinal dissociation. [ABSTRACT FROM AUTHOR]

Idiopathic ventricular fibrillation (IVF) causes sudden death in young adult patients without structural or ischemic heart disease. Most IVF cases are sporadic and some patients present with short-coupled torsade de pointes, the genetics of which are poorly understood. A man who had a first syncope at the age of 35 presented with frequent short-coupled premature ventricular beats with bursts of polymorphic ventricular tachycardia and then died suddenly. By exome sequencing, we identified three rare variants: p.I784F in the SPRY1 of the ryanodine receptor 2 (RyR2), p.A96S in connexin 40 (Cx40), reported to affect electrical coupling and cardiac conduction, and a nonsense p.R244X in the cardiac-specific troponin I-interacting kinase (TNNI3K). We assessed intracellular Ca2+ handling in WT and mutant human RYR2 transfected HEK293 cells by fluorescent microscopy and an enhanced store overload-induced Ca2+ release in response to cytosolic Ca2+ was observed in RyR2-I784F cells. In addition, crystal structures and thermal melting temperatures revealed a conformational change in the I784F-SPRY1 domain compared to the WT-domain. The novel RyR2-I784F variant in SPRY1 domain causes a leaky channel under non-stress conditions. The presence of several variants affecting Ca2+ handling and cardiac conduction suggests a possible oligogenic origin for the ectopies originating from Purkinje fibres. [ABSTRACT FROM AUTHOR]

Activation of the parasympathetic nervous system has been reported to have an antiarrhythmic role during ischemia–reperfusion injury by decreasing the arrhythmia triggers. Furthermore, it was reported that the parasympathetic neurotransmitter acetylcholine is able to modulate the ATP-dependent potassium current (IK-ATP), a crucial current activated during hypoxia. However, the possible significance of this current modulation in the antiarrhythmic mechanism is not fully clarified. Action potentials were measured using the conventional microelectrode technique from canine left ventricular papillary muscle and free-running Purkinje fibers, under normal and hypoxic conditions. Ionic currents were measured using the whole-cell configuration of the patch-clamp method. Acetylcholine at 5 μmol/L did not influence the action potential duration (APD) either in Purkinje fibers or in papillary muscle preparations. In contrast, it significantly lengthened the APD and suppressed the Purkinje–ventricle APD dispersion when it was administered after 5 μmol/L pinacidil application. Carbachol at 3 μmol/L reduced the pinacidil-activated IK-ATP under voltage-clamp conditions. Acetylcholine lengthened the ventricular action potential under simulated ischemia condition. In this study, we found that acetylcholine inhibits the IK-ATP and thus suppresses the ventricle–Purkinje APD dispersion. We conclude that parasympathetic tone may reduce the arrhythmogenic substrate exerting a complex antiarrhythmic mechanism during hypoxic conditions. [ABSTRACT FROM AUTHOR]

Ibuprofen is a widely used nonsteroidal anti-inflammatory drug, which has recently been associated with increased cardiovascular risk, but its electrophysiological effects have not yet been properly studied in isolated cardiac preparations. We studied the effects of ibuprofen on action potential characteristics and several transmembrane ionic currents using the conventional microelectrode technique and the whole-cell configuration of the patch-clamp technique on cardiac preparations and enzymatically isolated ventricular myocytes. In dog (200 µM; n = 6) and rabbit (100 µM; n = 7) papillary muscles, ibuprofen moderately but significantly prolonged repolarization at 1 Hz stimulation frequency. In dog Purkinje fibers, repolarization was abbreviated and maximal rate of depolarization was depressed in a frequency-dependent manner. Levofloxacin (40 µM) alone did not alter repolarization, but augmented the ibuprofen-evoked repolarization lengthening in rabbit preparations (n = 7). In dog myocytes, ibuprofen (250 µM) did not significantly influence IK1, but decreased the amplitude of Ito and IKr potassium currents by 28.2% (60 mV) and 15.2% (20 mV), respectively. Ibuprofen also depressed INaL and ICa currents by 19.9% and 16.4%, respectively. We conclude that ibuprofen seems to be free from effects on action potential parameters at lower concentrations. However, at higher concentrations it may alter repolarization reserve, contributing to the observed proarrhythmic risk in patients. [ABSTRACT FROM AUTHOR]

Increased transmural dispersion of repolarization is an established contributing factor to ventricular tachyarrhythmias. In this study, we evaluated the effect of chronic amiodarone treatment and acute administration of dofetilide in canine cardiac preparations containing electrotonically coupled Purkinje fibers (PFs) and ventricular muscle (VM) and compared the effects to those in uncoupled PF and VM preparations using the conventional microelectrode technique. Dispersion between PFs and VM was inferred from the difference in the respective action potential durations (APDs). In coupled preparations, amiodarone decreased the difference in APDs between PFs and VM, thus decreasing dispersion. In the same preparations, dofetilide increased the dispersion by causing a more pronounced prolongation in PFs. This prolongation was even more emphasized in uncoupled PF preparations, while the effect in VM was the same. In uncoupled preparations, amiodarone elicited no change on the difference in APDs. In conclusion, amiodarone decreased the dispersion between PFs and VM, while dofetilide increased it. The measured difference in APD between cardiac regions may be the affected by electrotonic coupling; thus, studying PFs and VM separately may lead to an over- or underestimation of dispersion. [ABSTRACT FROM AUTHOR]

His‐Purkinje conduction system pacing (HPCSP) in the form of His bundle pacing (HBP) and left bundle branch pacing (LBBP) allows normal left ventricular activation, thereby preventing the adverse consequences of right ventricular pacing. HBP has been established for several years with centers from China, Europe, and North America reporting their experience. There is international guidance as to how to implant such systems with the differing patterns of His bundle capture clearly described. LBBP is a more recent innovation with potential advantages including improved pacing parameters. HPCSP has been extensively studied in a variety of indications including cardiac resynchronization therapy, atrioventricular node ablation, and bradycardia pacing. This review will focus on the clinical outcomes of HPCSP including mortality and morbidity of heart failure hospitalization and symptoms. [ABSTRACT FROM AUTHOR]

A 10-years-old boy presented with a history of effort intolerance and palpitations for 4 months. His electrocardiogram showed wide complex tachycardia suggestive of fascicular ventricular tachycardia (VT). The echocardiogram showed moderate-to-severe left ventricular systolic dysfunction without any structural lesion. The tachycardia was unresponsive to adenosine and direct current cardioversion. It responded to oral verapamil. The electrophysiology study confirmed the tachycardia as left posterior fascicular VT. The tachycardia was successfully ablated guided by Purkinje potential on three-dimensional mappings. He showed improvement in ventricular functions before discharge. He is doing well on short-term follow-up. [ABSTRACT FROM AUTHOR]

It is important to know the morphological structure of the heart, which is a vital organ of the body, in detail. For this reason, we aimed to examine the morphological structure of the Saanen goat heart using light and scanning electron microscopy (SEM). A total of thirteen Saanen goat hearts were used in the study. To demonstrate the histological structure of the heart, samples taken from 9 hearts were fixed in 10% formaldehyde solution and blocked in paraffin after routine histological procedures. Histological staining was performed on the sections taken from the blocks. Four hearts were fixed in a 2.5% glutaraldehyde solution for electron microscopic examination. The samples taken were dehydrated with different concentrations of acetone, treated with osmium tetroxide, and critical point dried in accordance with SEM procedures. After being coated with gold/palladium (Au/Pd), samples were made ready for imaging under SEM. The general structure of the heart was determined in detail with histological and SEM examination. Although the structural findings of the Saanen goat heart were generally similar to findings in the literature, the shapes of the cells that formed the Purkinje fiber networks in SEM examination were different from other species. It is thought that the images obtained will help in studies of the morphological structure of the heart and in detecting pathological changes that may occur in the heart. [ABSTRACT FROM AUTHOR]

Modeling of human organs has long been a task for scientists in order to lower the costs of therapeutic development and understand the pathological onset of human disease. For decades, despite marked differences in genetics and etiology, animal models remained the norm for drug discovery and disease modeling. Innovative biofabrication techniques have facilitated the development of organ-on-a-chip technology that has great potential to complement conventional animal models. However, human organ as a whole, more specifically the human heart, is difficult to regenerate in vitro , in terms of its chamber specific orientation and its electrical functional complexity. Recent progress with the development of induced pluripotent stem cell differentiation protocols, made recapitulating the complexity of the human heart possible through the generation of cells representative of atrial & ventricular tissue, the sinoatrial node, atrioventricular node and Purkinje fibers. Current heart-on-a-chip approaches incorporate biological, electrical, mechanical, and topographical cues to facilitate tissue maturation, therefore improving the predictive power for the chamber-specific therapeutic effects targeting adult human. In this review, we will give a summary of current advances in heart-on-a-chip technology and provide a comprehensive outlook on the challenges involved in the development of human physiologically relevant heart-on-a-chip. Unlabelled Image [ABSTRACT FROM AUTHOR]

The human heart beats around 2.5 billion times during a normal lifetime. Responsible for this function is the cardiac conduction system (CCS). This unique system is formed by specialized cardiomyocites, in which generate the cardiac impulse and conduct it from the atrial to the ventricular chambers. The functional components of the CCS are: sinoatrial node (SAN), atrioventricular node(AVN), atrioventricular bundle (AVB or bundle of His), the right and the left bundle branches (RBB and LBB) and the Purkinje network fibers. The CCS examination is a difficult task for most practicing pathologists, because it is macroscopically identical to the surrounding cardiac structures. For this reason,detailed anatomical knowledge is required to identify it. [ABSTRACT FROM AUTHOR]

Background: Repetitive monomorphic ventricular tachycardia (RMVT) arising from the left His‐Purkinje system can occasionally be encountered during clinical practice. We describe eight cases as a unique entity in this study to characterize the clinical and electrophysiological features of the patients. Methods: Eight patients with frequent palpitation (five men with median age of 28 years) were included in the study from January 2003 to July 2018. Twelve‐lead ECG (Electrocardiogram), Holter, and echocardiographic tests were performed after medical history interrogations and physical examinations. Antiarrhythmic drug therapy was essential to all patients, and catheter ablation was attempted if the patients could not tolerate or were not responsive to drug therapy. Results: No patients had a history of syncope and a family history of sudden cardiac death. ECGrecording was characterized by frequent ventricular extrasystoles, ventricular couplets, and salvos of nonsustained VT competitive with sinus rhythm. The QRS morphology of ectopic beats was in the right bundle branch block pattern with severe left axis deviation. The width of the QRS complex from ECG was 135 ms (120‐140) during ventricular tachycardia. Verapamil had no effect on all VT individuals. Enlargement of the left ventricle was found in two patients. Four out of six cases were successful with catheter ablation treatment. Conclusion: RMVT arising from the left His‐Purkinje system is a special arrhythmic and nonverapamil‐sensitive entity. The electrophysiological mechanism of this treatment appears to be focal firing, which is amendable to catheter ablation in symptomatic and high‐burden patients. [ABSTRACT FROM AUTHOR]

The Cardiac Purkinje Fiber (CPF) is the last branch of the heart conduction system, which is meshed with the normal ventricular myocyte. Purkinje fiber plays a key role in the occurrence of ventricular arrhythmia and maintenance. Does the heart Purkinje fiber cells have the same memory function as the cerebral nerve? In this paper, the cardiac Hodgkin–Huxley equation is taken as the object of study. In particular, we find that the potassium ion-channel K and the sodium ion-channel N a are memristors. We also derive the small-signal equivalent circuits about the equilibrium points of the CPF Hodgkin–Huxley model. According to the principle of local activity, the regions of Locally-Active domain, Edge of Chaos domain and Locally-Passive domain are partitioned under parameters (a , b) , and the domain exhibiting the normal human heartbeat frequency range (Goldilocks Zone) is identified. Meanwhile, the Super-Critical Hopf bifurcation of the CPF Hodgkin–Huxley model is identified. Finally, the migration changes between different state domains under external current I ext excitation are analyzed in detail. All of the above complex nonlinear dynamics are distilled and mapped geometrically into a surreal union of intersecting two-dimensional manifolds, dubbed the Hodgkin–Huxley'smagic roof. [ABSTRACT FROM AUTHOR]

Introduction. Purkinje system and false tendons (FTs) are related to ventricular arrhythmia, but the association between Purkinje fibers and FTs is not clear. This study investigated the associations of anatomical and electrophysiological characteristics between Purkinje fibers and FTs. Methods and Results. We optimized the protocol of Lugol's iodine solution staining of Purkinje fibers to study the anatomical structure and originated a novel electrophysiological mapping method, named the direct visual mapping (DVM) method, to study the electrophysiological characteristics. By using the above-mentioned innovations in 12 dogs, we found the following. (1) There was no Purkinje fiber found 0.5 cm–1.0 cm below the valve annulus or on the leaflets or chordae tendineae of the mitral valve or adjacent to the top 1/3 of the papillary muscle. (2) Purkinje fibers existed in all FTs, including smaller and tiny FTs. (3) The Purkinje fibers contained in the FTs extended from the proximal to the distal end, and their electrophysiological characteristics were similar to the fibers on the endocardium, including anterograde, retrograde, and decremental conduction and automaticity. Conclusions. Purkinje fibers are commonly found in FTs. The electrophysiological characteristics of the Purkinje fibers contained in FTs are similar to the fibers on the endocardium. FTs might have an anatomical and electrophysiological basis for ventricular arrhythmia. [ABSTRACT FROM AUTHOR]

Cardiac arrhythmias significantly contribute to mortality in Duchenne muscular dystrophy (DMD), a degenerative muscle disease triggered by mutations in the gene encoding for the intracellular protein dystrophin. A major source for the arrhythmias in patients with DMD is impaired ventricular impulse conduction, which predisposes for ventricular asynchrony, decreased cardiac output, and the development of reentrant mechanisms. The reason for ventricular conduction impairments and the associated arrhythmias in the dystrophic heart has remained unidentified. In the present study, we explored the hypothesis that dystrophin-deficient cardiac Purkinje fibers have reduced Na+ currents (INa), which would represent a potential mechanism underlying slowed ventricular conduction in the dystrophic heart. Therefore, by using a Langendorff perfusion system, we isolated Purkinje fibers from the hearts of adult wild-type control and dystrophin-deficient mdx mice. Enhanced green fluorescent protein (eGFP) expression under control of the connexin 40 gene allowed us to discriminate Purkinje fibers from eGFP-negative ventricular working cardiomyocytes after cell isolation. Finally, we recorded INa from wild-type and dystrophic mdx Purkinje fibers for comparison by means of the whole cell patch clamp technique. We found substantially reduced INa densities in mdx compared with wild-type Purkinje fibers, suggesting that dystrophin deficiency diminishes INa. Because Na+ channels in the Purkinje fiber membrane represent key discriminates of ventricular conduction velocity, we propose that reduced INa in Purkinje fibers at least partly explains impaired ventricular conduction and the associated arrhythmias in the dystrophic heart. NEW & NOTEWORTHY Dystrophic cardiac Purkinje fibers have abnormally reduced Na+ current densities. This explains impaired ventricular conduction in the dystrophic heart. [ABSTRACT FROM AUTHOR]

Aims: His‐Purkinje system pacing has been demonstrated as a synchronized ventricular pacing strategy via pacing His‐Purkinje system directly, which can decrease the incidence of adverse cardiac structure alteration compared with right ventricular pacing (RVP). The purpose of this meta‐analysis was to compare the effects of His‐Purkinje system pacing and RVP in patients with bradycardia and cardiac conduction dysfunction. Methods: PubMed, Embase, Cochrane Library, and Web of Science were systematically searched from the establishment of databases up to 15 December 2019. Studies on long‐term clinical outcomes of His‐Purkinje system pacing and RVP were included. Chronic paced QRS duration, chronic pacing threshold, left ventricular ejection fraction (LVEF), left ventricular end‐diastolic volume (LVEDV), left ventricular end‐systolic volume (LVESV), all‐cause mortality, and heart failure hospitalization were collected for meta‐analysis. Results: A total of 13 studies comprising 2348 patients were included in this meta‐analysis. Compared with RVP group, patients receiving His‐Purkinje system pacing showed improvement of LVEF (mean difference [MD], 5.65; 95% confidence interval [CI], 4.38‐6.92), shorter chronic paced QRS duration (MD, − 39.29; 95% CI, − 41.90 to − 36.68), higher pacing threshold (MD, 0.8; 95% CI, 0.71‐0.89) and lower risk of heart failure hospitalization (odds ratio [OR], 0.65; 95% CI, 0.44‐0.96) during the follow‐up. However, no statistical difference existed in LVEDV, LVESV and all‐cause mortality between the two groups. Conclusion: Our meta‐analysis suggests that His‐bundle pacing is more suitable for the treatment of patients with bradycardia and cardiac conduction dysfunction. [ABSTRACT FROM AUTHOR]

Introduction: The application of brief high voltage electrical pulses to tissue can lead to an irreversible or reversible electroporation effect in a cell-specific manner. In the management of ventricular arrhythmias, the ability to target different tissue types, specifically cardiac conduction tissue (His-Purkinje System) vs. cardiac myocardium would be advantageous. We hypothesize that pulsed electric fields (PEFs) can be applied safely to the beating heart through a catheter-based approach, and we tested whether the superficial Purkinje cells can be targeted with PEFs without injury to underlying myocardial tissue. Methods: In an acute (n = 5) and chronic canine model (n = 6), detailed electroanatomical mapping of the left ventricle identified electrical signals from myocardial and overlying Purkinje tissue. Electroporation was effected via percutaneous catheter-based Intracardiac bipolar current delivery in the anesthetized animal. Repeat Intracardiac electrical mapping of the heart was performed at acute and chronic time points; followed by histological analysis to assess effects. Results: PEF demonstrated an acute dose-dependent functional effect on Purkinje, with titration of pulse duration and/or voltage associated with successful acute Purkinje damage. Electrical conduction in the insulated bundle of His (n = 2) and anterior fascicle bundle (n = 2), was not affected. At 30 days repeat cardiac mapping demonstrated resilient, normal electrical conduction throughout the targeted area with no significant change in myocardial amplitude (pre 5.9 ± 1.8 mV, 30 days 5.4 ± 1.2 mV, p = 0.92). Histopathological analysis confirmed acute Purkinje fiber targeting, with chronic studies showing normal Purkinje fibers, with minimal subendocardial myocardial fibrosis. Conclusion: PEF provides a novel, safe method for non-thermal acute modulation of the Purkinje fibers without significant injury to the underlying myocardium. Future optimization of this energy delivery is required to optimize conditions so that selective electroporation can be utilized in humans the treatment of cardiac disease. [ABSTRACT FROM AUTHOR]

The article presents architecture of the cardiac conduction system beginning with the atrioventricular (AV) bundle and ending in the filigree‐like interwoven distal Purkinje system. Positional variation, alignment of the electrodes, and changes in the conduction tissue itself at the site of stimulation or downstream overtime create complexity.