Cardiac Corpuscles: A "New" Morphofunctional Entity? / Corpúsculos Cardíacos: ¿Una "Nueva" Entidad Morfofuncional?

SUMMARY: 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 micro- plastination (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.

La existencia de "estructuras musculares de transición" entre los ramos subendocárdicos (fibras de Purkinje) y las fibras musculares ventriculares activas(FMV) fue descrita por primera vez por el anatomista alemán Kurt Goerttler en 1964, quien las denominó "órganos del núcleo subendocárdico". Supuso que tales fibras funcionaban como mecanoreceptores, controlando la intensidad de la contracción de la musculatura ventricular. El anatomista brasileño Ferraz de Carvalho describió estructuras similares en 1993. Una búsqueda bibliográfica exhaustiva no logró identificar ningún otro artículo de investigación que confirmara o negara su existencia. El objetivo de este trabajo fue encontrar dichas estructuras en las paredes ventriculares subendocárdicas de corazones humanos. Recolectamos 15 corazones conservados en formalina del Departamento de Anatomía de la Universidad de São Paulo y seccionamos las porciones apicales de los ventrículos derecho e izquierdo según el método utilizado por Goerttler. Utilizamos histología convencional (microscopía de luz-LM), microscopía electrónica de barrido (SEM) y un nuevo método de conservación llamado microplastinación (MP). En la pared anterior del ventrículo derecho en la región subendocárdica entre el tabique interventricular y la banda moderadora, encontramos varios haces de fibras fusiformes y helicoidales de histología similar a la FMV. Los haces medían entre 400 y 1150 µm de longitud y estaban separados de las fibras musculares adyacentes por una fina fibra de colágeno, actuando así como una "pseudocápsula". Algunas estructuras parecían estar vinculadas a la fibras de purkinje y parecían ser vasos linfáticos, sanguíneos y nerviosos. Llamamos a esas estructuras "corpúsculos cardíacos" (CC). La observación del CC previamente "desconocido" en este estudio inicial confirmó las descripciones anteriores y su descubrimiento puede contribuir a nuevas perspectivas en el estudio de la estructura y función del músculo cardíaco.

Crista Supraventricularis Purkinje Network and Its Relation to Intraseptal Purkinje Network.

Using transparent specimens with a dual color injection, microscopy, and computer tomography, this report shows that the right and left ventricular subendocardial Purkinje networks are connected by an extensive septal network in the bovine heart. The septal network is present along the entire septum except at a free zone below ventricular valves. Being the only communication of the basal right septum with the right free wall, the supraventricular crest is an enigmatic but not, by any means, hidden muscular structure. It is one of the last structures to be activated in human heart. It is shown here that the supraventricular crest Purkinje network connects the anterosuperior right ventricular basal free wall Purkinje network to anterior right ventricular basal septal Purkinje network. It is suggested that the stimulus initiated at middle left ventricular endocardium will activate the supraventricular crest. The intraseptal connection found between the basal left ventricular subendocardial septal Purkinje network and the right ventricular basal septal Purkinje network is, probably, the pathway for the stimulus. An anatomic basis is provided to explain why the inflow tract contracts earlier than the outflow tract in the right ventricle systole. Anat Rec, 2017. © 2017 Wiley Periodicals, Inc. Anat Rec, 300:1793-1801, 2017. © 2017 Wiley Periodicals, Inc.

Continuous-time control of alternans in long Purkinje fibers.

Alternans-an arrhythmic response of cardiac tissue to periodic pacing-often serves as a precursor to a more dangerous, and potentially lethal, state of fibrillation. Suppression of alternans using feedback control may be a plausible method to prevent fibrillation. Several approaches based on impulsive control have been proposed previously, where feedback is applied for a brief instance of time during each pacing interval. This paper presents a continuous-time approach, where feedback current is applied at all times, which is capable of suppressing alternans in fibers of significantly greater length (up to at least 4 cm), compared with impulsive control (less than 1 cm), and for a wide range of pacing cycle lengths.

In silico ischaemia-induced reentry at the Purkinje-ventricle interface.

AIMS: This computational modelling work illustrates the influence of hyperkalaemia and electrical uncoupling induced by defined ischaemia on action potential (AP) propagation and the incidence of reentry at the Purkinje-ventricle interface in mammalian hearts. METHODS AND RESULTS: Unidimensional and bidimensional models of the Purkinje-ventricle subsystem, including ischaemic conditions (defined as phase 1B) in the ventricle and an ischaemic border zone, were developed by altering several important electrophysiological parameters of the Luo-Rudy AP model of the ventricular myocyte. Purkinje electrical activity was modelled using the equations of DiFrancesco and Noble. Our study suggests that an extracellular potassium concentration [K(+)]o >14 mM and a slight decrease in intercellular coupling induced by ischaemia in ventricle can cause conduction block from Purkinje to ventricle. Under these conditions, propagation from ventricle to Purkinje is possible. Thus, unidirectional block (UDB) and reentry can result. When conditions of UDB are met, retrograde propagation with a long delay (320 ms) may re-excite Purkinje cells, and give rise to a reentrant pathway. This induced reentry may be the origin of arrhythmias observed in phase 1B ischaemia. CONCLUSION: In a defined setting of ischaemia (phase 1B), a small amount of uncoupling between ventricular cells, as well as between Purkinje and ventricular tissue, may induce UDBs and reentry. Hyperkalaemia is also confirmed to be an important factor in the genesis of reentrant rhythms, since it regulates the range of coupling in which UDBs may be induced.

Alpha-mannosidosis in goats caused by the swainsonine-containing plant Ipomoea verbascoidea.

A disease of the nervous system is reported in goats in the semiarid region of northeastern Brazil. Histological examination showed diffuse vacuolation of neurons and epithelial cells of the pancreas, thyroid, renal tubules, and liver. The swainsonine-containing plant Ipomoea verbascoidea was found on both farms where the goats originated. This plant was experimentally administered to 3 goats, inducing clinical signs and histologic lesions similar to those observed in spontaneous cases. On the lectin histochemical analysis, cerebellar cells and pancreatic acinar cells gave positive reactions to Triticum vulgaris agglutinin (WGA), succinylated Triticum vulgaris agglutinin (sWGA), Lens culinaris agglutinin (LCA), Canavalia ensiformis agglutinin (ConA), Pisum sativum agglutinin (PSA), Ricinus communis agglutinin (RCA(120)), Arachis hypogaea agglutinin (PNA), and Phaseolus vulgaris erythroagglutinin (PHA-E) suggesting storage of α-fucose, α-D-mannose, α-D-glucose, ß-D-N-acetyl-glucosamine, N-acetyl-galactosamine, and acetyl-neuraminic acid. This pattern of lectin staining partially agrees with results previously reported for poisoning by swainsonine-containing plants. The chemical analysis of dried leaves of I. verbascoidea detected swainsonine (0.017%), calystegine B(1) (0.16%), calystegine B(2) (0.05%), and calystegine C(1) (0.34%). It is concluded that I. verbascoidea causes α-mannosidosis in goats.

The enigmatic sixth wave of the electrocardiogram: the U wave.

The U wave is the last, inconstant, smallest, rounded and upward deflection of the electrocardiogram. Controversial in origin, it is sometimes seen following the T wave with the TU junction along the baseline or fused with it and before P of the following cycle on the TP segment. In this review we will study its temporal location related to monophasic action potential, cardiac cycle and heart sounds, polarity, voltage or amplitude, frequency and shapecontour. We will analyze the clinical significance of negative, alternant, prominent U wave, and the difference between T wave with two peaks (T1-T2) and true U wave. Finally we will analyze the four main hypotheses about the source of U wave: repolarization of the intraventricular conducting system or Purkinje fibers system, delayed repolarization of the papillary muscles, afterpotentials caused by mechanoelectrical hypothesis or mechanoelectrical feedback, and the prolonged repolarization in the cells of the mid-myocardium ("M-cells").

Arritmias y muerte súbita en la taquicardia ventricular catecolaminérgica de origen hereditario / Ventricular arrhythmias of catecholaminergic origin and sudden death

The hereditary disease known as polymorphic catecholaminergic ventricular tachycardia (PCVT) is highly lethal. Almost 30% of the affected patients die before 40 years old, mainly due to sudden cardiac death. We have used isolated hearts from mutant mice (type 2 ryanodine receptors, RyR2/RyR2(R4496C)) to investigate arrhythmia mechanisms that are adrenergic- and intracellular calcium ([Ca2+]o) levels-dependent. Our results corroborate that polymorphic and bidirectional ventricular arrhythmias, as well as ventricular fibrillation, occurs in 50% of RyR2/ RyR2(R4496C) mice, and in less than 12% of the non-affected mice. Our hypothesis suggests that the origin of catecholaminergic arrhythmias in animals, and possibly in humans, is conditioned by the focal activity that begins by late post-potentials in the Purkinje fibers.

[Ventricular arrhythmias of catecholaminergic origin and sudden death]. / Arritmias y muerte súbita en la taquicardia ventricular catecolaminérgica de origen hereditario.

The hereditary disease known as polymorphic catecholaminergic ventricular tachycardia (PCVT) is highly lethal. Almost 30% of the affected patients die before 40 years old, mainly due to sudden cardiac death. We have used isolated hearts from mutant mice (type 2 ryanodine receptors, RyR2/RyR2(R4496C)) to investigate arrhythmia mechanisms that are adrenergic- and intracellular calcium ([Ca2+]o) levels-dependent. Our results corroborate that polymorphic and bidirectional ventricular arrhythmias, as well as ventricular fibrillation, occurs in 50% of RyR2/ RyR2(R4496C) mice, and in less than 12% of the non-affected mice. Our hypothesis suggests that the origin of catecholaminergic arrhythmias in animals, and possibly in humans, is conditioned by the focal activity that begins by late post-potentials in the Purkinje fibers.

[Double tachyarrhythmia: left anterior fascicular ventricular tachycardia associated with atrial flutter and fibrillation. Report of a case]. / Doble taquiarritmia: taquicardia ventricular fascicular anterior izquierda asociada a fibrilación y flutter auriculares. Reporte de un caso.

A patient with episodes of palpitation in whom the electrocardiogram showed a right bundle branch (RBBB) configuration and right axis deviation underwent electrophysiologic study and radiofrequency ablation. Left ventricular endocardial mapping during ventricular tachycardia (VT) identified the earliest ventricular activation in the anterolateral wall of the left ventricle. The fused Purkinje potential was recorded at that site, and preceded the QRS complex by 47 mseg, with pace mapping showing an optimal match between the paced rhythm and the clinical VT. The stimulus to QRS time was equal to the Purkinje potential-QRS time. Several radiofrequency lesions were applied in this region, one of them resulted with termination of the tachycardia. Following delivery of this lesion the ventricular tachycardia couldn't be induced either at baseline or during isoproterenol infusion. During VT, atrial fibrillation and atrial flutter were observed, cardioversion was performed reverting to sinus rhythm.

Antiarrhythmic and electrophysiological effects of the novel KATP channel opener, rilmakalim, in rabbit cardiac cells.

1. The effects of rilmakalim, a potassium channel opener, were studied on rabbit cardiac Purkinje, ventricular muscle and atrial fibers, with the use of conventional microelectrode techniques. 2. Rilmakalim (0.24-7.2 microM) shortened, in a concentration-dependent manner, the action potential duration (APD) in Purkinje and ventricular muscle without affecting other parameters of the action potential. Pinacidil (30-300 microM) also decreased the APD of Purkinje fibers. 3. Rilmakalim (2.4 microM) and cromakalim (100 microM) hyperpolarized and abolished abnormal automaticity of cardiac Purkinje fibers pretreated with barium (0.2-0.3 mM). Glibenclamide (5 microM) blocked the hyperpolarizing effect. 4. Stable early afterdepolarizations induced in Purkinje fibers by berberine (100 microM) were reversibly blocked by rilmakalim (2.4 microM), which also suppressed late afterdepolarizations induced in Purkinje fibers treated with ouabain (0.3-0.5 microM). 5. The rate of spontaneous discharges of the rabbit sinoatrial node was not affected by rilmakalim (7.2 microM) or by pinacidil (100 microM). Both agents were also unable to affect the APD of atrial muscle fibers. 6. In cardiac Purkinje fibers, tetraethylammonium (TEA; 20 mM) significantly reduced the effects of rilmakalim (2. 4 microM) on the APD. However, neither TEA nor glibenclamide (100 microM) reduced the shortening of the APD induced by dinitrophenol (30 microM) or by salicylate (1 mM).

[Mechanisms and dynamics of episodes of progression of of 2:1 atrioventricular to high degree atrioventricular block]. / Mecanismos e dinâmica da progressão dos episódios de bloqueio atrioventricular 2:1 para bloqueio atrioventricular de alto grau.

PURPOSE: To evaluate the mechanisms and dynamics of episodes of progression to high degree (HD) atrioventricular (AV) block (B) analyzed during incremental atrial pacing (St), in patients with previous 2:1 His-Purkinje (HP) AVB. METHODS: Data from 4 patients were analyzed. All of them with history of syncope and ECG exhibiting 2:1 AVB with wide QRS pattern. The AVB was in the HP system (HPS) in all. Every patient was submitted to electrophysiologic study with incremental atrial pacing, by which the conduction sequences and the AV conduction ratios (AVR) were analyzed. The basal (B) cycle length (CL) was defined as the shortest interval between two conducted beats (spontaneous or pacing-induced). The incremental atrial stimulation was performed beginning with CL 10 msec shorter than BCL until reaching 250 msec. RESULTS: Nineteen episodes of progression to HD-AVB were seen. A) With StCL between 31 and 26% of BCL, AVR were 3:1, 4:1 and 5:1, with only one blocking zone (BZ) in the HPS; B) with StCL between 24 and 22% of BCL, AVR were 5:1, 7:2, 9:2e11:3. In this situation a 2nd BZ ensues-on proximal, site of a decremental conduction, situated in the AV node (AVN) or in the HPS, and the other (distal level) always in HPS; C) with StCL between 24 and 16% of BCL, AVR were 5:1, 6:1, 10:2, 11:2 and 12:3. Here, these AVR were explained by postulating 3 BZ where 2 were in AVN and 1 in HPS, or inversely with 1 in AVN and 2 in HPS. The decremental conduction occurred in 1 or 2 out 3 BZ and an integral conduction (like 2:1 or 3:1) in the others. CONCLUSION: The BCL is the determinant of the AVR observed. As the StCL is shortened (< 26% BCL) a 2nd or 3rd BZ in the AVN or in the HPS ensues. These observations suggest that the mechanisms and dynamics of progression to HD-AVB apply only during incremental atrial pacing and there is a clear difference with what has been observed with the progression occurring exclusively at AV node.

Mecanismos e dinâmica da progressão dos episódios de bloqueio atrioventricular 2: 1 para bloqueio atrioventricular de alto grau / Mechanisms and dynamics of episades of progression of 2:1 A-V block to high degree A-V

PURPOSE--To evaluate the mechanisms and dynamics of episodes of progression to high degree (HD) atrioventricular (AV) block (B) analyzed during incremental atrial pacing (St), in patients with previous 2:1 His-Purkinje (HP) AVB. METHODS--Data from 4 patients were analyzed. All of them with history of syncope and ECG exhibiting 2:1 AVB with wide QRS pattern. The AVB was in the HP system (HPS) in all. Every patient was submitted to electrophysiologic study with incremental atrial pacing, by which the conduction sequences and the AV conduction ratios (AVR) were analyzed. The basal (B) cycle length (CL) was defined as the shortest interval between two conducted beats (spontaneous or pacing-induced). The incremental atrial stimulation was performed beginning with CL 10 msec shorter than BCL until reaching 250 msec. RESULTS--Nineteen episodes of progression to HD-AVB were seen. A) With StCL between 31 and 26 of BCL, AVR were 3:1, 4:1 and 5:1, with only one blocking zone (BZ) in the HPS; B) with StCL between 24 and 22 of BCL, AVR were 5:1, 7:2, 9:2e11:3. In this situation a 2nd BZ ensues-on proximal, site of a decremental conduction, situated in the AV node (AVN) or in the HPS, and the other (distal level) always in HPS; C) with StCL between 24 and 16 of BCL, AVR were 5:1, 6:1, 10:2, 11:2 and 12:3. Here, these AVR were explained by postulating 3 BZ where 2 were in AVN and 1 in HPS, or inversely with 1 in AVN and 2 in HPS. The decremental conduction occurred in 1 or 2 out 3 BZ and an integral conduction (like 2:1 or 3:1) in the others. CONCLUSION--The BCL is the determinant of the AVR observed. As the StCL is shortened (< 26 BCL) a 2nd or 3rd BZ in the AVN or in the HPS ensues. These observations suggest that the mechanisms and dynamics of progression to HD-AVB apply only during incremental atrial pacing and there is a clear difference with what has been observed with the progression occurring exclusively at AV node.

Efectos de la adenosina sobre el automatismo y las oscilaciones post-potencial en fibras de Purkinje de mamífero / The effects of adenosine on automacity and after potential oscillations on canine cardiac Purkinje fibers

Se estudiaron los efectos de la adenosina (ADO) sobre el automatismo y las oscilaciones post-potencial de fibras de Purkinje de corazones de perro. Se emplearon concentraciones de ADO desde 10-8 hasta 10-5 M. Se obtuvieron registros de la actividad eléctrica celular mediante microelectrodos. La ADO en concentraciones mayores de 10-8 M produce durante los dos primeros minutos un incremento súbito de la longitud del ciclo básico (LCB), de alrededor del 50 por ciento de su valor control, lo que después progresa hacia un estado estable. La curva dosis-respuesta en la fase estable es sigmoidal típica y semeja a las curvas de ocupación de receptores. Las pendientes del potencial de marcadores tienden a disminuir junto con la depresión de la LCB. Las oscilaciones post-potencial inducidas por tener de estimulación muestran que la pendiente de despolarización de la oscilación post-potencial disminuye con ADO 10-8 M pero no con concentraciones mayores. Los resultados encontrados sugieren que la ADO provoca un incremento en la corriente de potasio tiempo independiente. Este efecto parece depender de la estimulación de receptores específicos. El que la adenosina tenga un curso temporal bifásico sugiere la existencia de receptores purinérgicos con afinidades y constantes de disociación distinta pero con efectos similares y que podrían ser subtipos de receptores A1

Fulguración de un foco extrasistólico ventricular / Catheter ablation of an extrasystolic ventricular focus

Se presenta un caso de extrasístoles ventriculares sintomáticas refractarias a antiarrítmicos, con morfología QRS de bloqueo de rama derecha y desviación axial izquierda en una mujer de 68 años sin cardiopatía estructural. El mapeo endocárdiaco del foco extrasistólico se localizó en la región meso-inferoapical del septum ventricular izquierdo sugiriendo un origen en la red de Purkinje de la subdivisión posterior izquierda. La ablación transcatéter con energía de corriente directa eliminó las extrasístoles, sin complicaciones del procedimiento y la paciente permaneció asintomática durante el seguimiento a 3 meses

[Effects of adenosine on automaticity and post-potential oscillations in Purkinje fibers of mammals]. / Efectos de la adenosina sobre el automatismo y las oscilaciones post-potencial en fibras de Purkinje de mamífero.

The aim of the present paper was to study the effects of adenosine (ADO) on automaticity and after potential oscillations on canine cardiac Purkinje fibers. ADO concentrations from 10(-8) to 10(-5) M were used. The intracellular electrical activity was recorded with conventional microelectrodes. ADO increased during the first two minutes the basic cycle length (BLC) with concentrations higher than 10(-8) M, to a value 50% above control, later there is a progression to a steady state. The dose-response curve in the steady state is sigmoidal and resembles those of receptor occupation. The slopes of pacemaker potentials have a tendency to decrease along with the increase in BLC length. After potential oscillations decrease with 10(-8) M of ADO but not with larger concentrations. There results supports the hypothesis that ADO produces an increase in the time independent potassium current similar to the one described for atrial and ventricular myocytes. This effect probably depends on specific receptor stimulation. The biphasic time course suggests the existence of subtypes of A1 receptor with different dissociation constants and affinities but with similar actions. The idea that the ADO effects depend mainly on the potassium currents and not on I(f) is supported by the absence of a dose-dependent effects in the oscillatory after potentials.

Subthreshold stimulation of Purkinje fibers interrupts ventricular tachycardia in intact hearts. Experimental study with voltage-sensitive dyes and imaging techniques.

The effects of subthreshold stimulation (STS) delivered during right atrial pacing and ventricular tachycardia (VT) were investigated in Langendorff-perfused guinea pig hearts. The hearts were stained with a voltage-sensitive dye (RH 421) to map the propagation of optical action potentials. Sustained VT was reliably induced by 5-second trains (cycle length [CL], 25 to 50 milliseconds; duration, 0.5 to 10 milliseconds; and voltage, 2x threshold voltage) of impulses (n = 12 hearts) or a single premature beat (n = 6). The location of extrastimuli was not critical to the induction of VT, but the diameter of the heart had to be > or = 14.5 mm. During VT, heart rate increased from 200 to 600 beats per minute; action potential durations decreased from 112 to 175 milliseconds to 60 to 105 milliseconds, with no diastolic interval. Activation on the epicardium spread anisotropically, but VT decreased the "apparent" maximum conduction velocity (theta max) by 68% and altered the orientation of the major axis from beat to beat. Activation patterns and theta max measured during VT were similar to patterns recorded during direct pacing of the ventricle and indicated that Purkinje fibers no longer propelled ventricular excitation. STS (CL, 25 to 50 milliseconds; duration, 0.5 to 25 milliseconds; and voltage, 0.5x to 0.8x threshold; trains of 2.0 to 2.5 seconds) interrupted VT when applied to Purkinje fibers lining the endocardium (n = 6) but failed to interrupt VT when applied to the epicardium (n = 8). In atrial pacing, STS delivered to the endocardium increased theta max from 2.44 +/- 0.32 (mean +/- SEM) to 3.63 +/- 0.21 m/s in a local region surrounding the first activation sites (n = 4). Alternatively, VT could be terminated by reducing theta max (approximately 55%) with procainamide (10 mumol/L) (n = 6). STS terminates VT by synchronizing ventricular excitation most likely by increasing local conduction and/or improving the coupling between Purkinje and ventricular cells.