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.

Unsolved Questions on the Anatomy of the Ventricular Conduction System

We reviewed the anatomical characteristics of the conduction system in the ventricles of human and ungulate hearts and then raised some questions to be answered by clinical and anatomical studies in the future. The ventricular conduction system is a 3-dimensional structure as compared to the 2-dimensional character of the atrial conduction system. The proximal part consisting of the atrioventricular node, the bundle of His and fascicles are groups of conducting cells surrounded by fibrous connective tissue so as to insulate from the underlying myocardium. Their location and morphological characters are well established. The bundle of His is a cord like structure but the left and right fascicles are broad at the proximal and branching at the distal part. The more distal part of fascicles and Purkinje system are linear networks of conducting cells at the immediate subendocardium but the intra-mural network is detected at the inner half of the ventricular wall. The papillary muscle also harbors Purkinje system not in the deeper part. It is hard to recognize histologically in human hearts but conducting cells as well as Purkinje cells are easily recognized in ungulate hearts. Further observation on human and ungulate hearts with myocardial infarct, we could find preserved Purkinje system at the subendocardium in contrast to the damaged system at the deeper myocardium. Further studies are necessary on the anatomical characteristics of this peripheral conduction system so as to correlate the clinical data on hearts with ventricular arrhythmias.

Comparison of electrophysiological effects of calcium channel blockers on cardiac repolarization

Dihydropyridine (DHP) calcium channel blockers (CCBs) have been widely used to treat of several cardiovascular diseases. An excessive shortening of action potential duration (APD) due to the reduction of Ca2+ channel current (I(Ca)) might increase the risk of arrhythmia. In this study we investigated the electrophysiological effects of nicardipine (NIC), isradipine (ISR), and amlodipine (AML) on the cardiac APD in rabbit Purkinje fibers, voltage-gated K+ channel currents (I(Kr), I(Ks)) and voltage-gated Na+ channel current (I(Na)). The concentration-dependent inhibition of Ca2+ channel currents (I(Ca)) was examined in rat cardiomyocytes; these CCBs have similar potency on I(Ca) channel blocking with IC50 (the half-maximum inhibiting concentration) values of 0.142, 0.229, and 0.227 nM on NIC, ISR, and AML, respectively. However, ISR shortened both APD50 and APD90 already at 1 microM whereas NIC and AML shortened APD50 but not APD90 up to 30 microM. According to ion channel studies, NIC and AML concentration-dependently inhibited I(Kr) and I(Ks) while ISR had only partial inhibitory effects (<50% at 30 microM). Inhibition of I(Na) was similarly observed in the three CCBs. Since the I(Kr) and I(Ks) mainly contribute to cardiac repolarization, their inhibition by NIC and AML could compensate for the AP shortening effects due to the block of I(Ca).

Cardiovascular Safety Pharmacology of Sibutramine

Sibutramine is an anorectic that has been banned since 2010 due to cardiovascular safety issues. However, counterfeit drugs or slimming products that include sibutramine are still available in the market. It has been reported that illegal sibutramine-contained pharmaceutical products induce cardiovascular crisis. However, the mechanism underlying sibutramine-induced cardiovascular adverse effect has not been fully evaluated yet. In this study, we performed cardiovascular safety pharmacology studies of sibutramine systemically using by hERG channel inhibition, action potential duration, and telemetry assays. Sibutramine inhibited hERG channel current of HEK293 cells with an IC50 of 3.92 muM in patch clamp assay and increased the heart rate and blood pressure (76 Deltabpm in heart rate and 51 DeltammHg in blood pressure) in beagle dogs at a dose of 30 mg/kg (per oral), while it shortened action potential duration (at 10 muM and 30 muM, resulted in 15% and 29% decreases in APD50, and 9% and 17% decreases in APD90, respectively) in the Purkinje fibers of rabbits and had no effects on the QTc interval in beagle dogs. These results suggest that sibutramine has a considerable adverse effect on the cardiovascular system and may contribute to accurate drug safety regulation.

Supraventricular Tachycardia and Sinus Rhythm with Contralateral Bundle Branch Block Patterns

A contralateral bundle branch block (BBB) aberration during tachycardia with a preexisting BBB strongly suggests the presence of ventricular tachycardia. We report on a middle-aged, female patient presented with wide QRS tachycardia. The patient had orthodromic atrioventricular tachycardia with a left BBB aberration in the presence of a preexisting right BBB due to an abnormal His-Purkinje system. We learned that the contralateral BBB aberration with supraventricular tachycardia could be seen when the His-Purkinje system was abnormal.

Electroanatomical Characteristics of Idiopathic Left Ventricular Tachycardia and Optimal Ablation Target during Sinus Rhythm: Significance of Preferential Conduction through Purkinje Fibers

PURPOSE: We hypothesized that Purkinje potential and their preferential conduction to the left ventricle (LV) posteroseptum during sinus rhythm (SR) are part of reentrant circuits of idiopathic left ventricular tachycardia (ILVT) and reentry anchors to papillary muscle. MATERIALS AND METHODS: In 14 patients with ILVT (11 men, mean age 31.5+/-11.1 years), we compared Purkinje potential and preferential conduction during SR with VT by non-contact mapping (NCM). If clear Purkinje potential(SR) was observed in the LV posteroseptum and the earliest activation site (EA) of preferential conduction at SR (EASR) was well matched with that of VT (EAVT), EASR was targeted for radiofrequency catheter ablation (RFCA). Also, the anatomical locations of successful ablation sites were evaluated by echocardiography in five additional patients. RESULTS: 1) All induced VTs exhibited clear Purkinje potential(VT) and preferential conduction in the LV posteroseptum. The Purkinje potential(VT) and EAVT was within 5.8+/-8.2 mm of EASR. However, the breakout sites of VT were separated by 30.2+/-12.6 mm from EAVT to the apical side. 2) Purkinje potential(SR) demonstrated a reversed polarity to Purkinje potential(VT), and the interval of Purkinje potential(SR)-QRS was longer than the interval of Purkinje potential(VT)-QRS (p<0.02) 3) RFCA targeting EASR eliminated VT in all patients without recurrence within 23.3+/-7.5 months, and the successful ablation site was discovered at the base of papillary muscle in the five additional (100%) patients. CONCLUSION: NCM-guided localization of EASR with Purkinje potential(SR) matches well with EAVT with Purkinje potential(VT) and provides an effective target for RFCA, potentially at the base of papillary muscle in patients with ILVT.

Effects of Mixed Herbal Extracts from Parched Puerariae Radix, Gingered Magnoliae Cortex, Glycyrrhizae Radix and Euphorbiae Radix (KIOM-79) on Cardiac Ion Channels and Action Potentials

KIOM-79, a mixture of ethanol extracts from four herbs (parched Puerariae radix, gingered Magnoliae cortex, Glycyrrhizae radix and Euphorbiae radix), has been developed for the potential therapeutic application to diabetic symptoms. Because screening of unexpected cardiac arrhythmia is compulsory for the new drug development, we investigated the effects of KIOM-79 on the action potential (AP) and various ion channel currents in cardiac myocytes. KIOM-79 decreased the upstroke velocity (Vmax) and plateau potential while slightly increased the duration of action potential (APD). Consistent with the decreased Vmax and plateau potential, the peak amplitude of Na+ current (INa) and Ca2+ current (ICa,L) were decreased by KIOM-79. KIOM-79 showed dual effects on hERG K+ current; increase of depolarization phase current (Idepol) and decreased tail current at repolarization phase (Itail). The increase of APD was suspected due to the decreased Itail. In computer simulation, the change of cardiac action potential could be well simulated based on the effects of KIOM-79 on various membrane currents. As a whole, the influence of KIOM-79 on cardiac ion channels are minor at concentrations effective for the diabetic models (0.1-10 microg/mL). The results suggest safety in terms of the risk of cardiac arrhythmia. Also, our study demonstrates the usefulness of the cardiac computer simulation in screening drug-induced long-QT syndrome.

Effects of Mixed Herbal Extracts from Parched Puerariae Radix, Gingered Magnoliae Cortex, Glycyrrhizae Radix and Euphorbiae Radix (KIOM-79) on Cardiac Ion Channels and Action Potentials

KIOM-79, a mixture of ethanol extracts from four herbs (parched Puerariae radix, gingered Magnoliae cortex, Glycyrrhizae radix and Euphorbiae radix), has been developed for the potential therapeutic application to diabetic symptoms. Because screening of unexpected cardiac arrhythmia is compulsory for the new drug development, we investigated the effects of KIOM-79 on the action potential (AP) and various ion channel currents in cardiac myocytes. KIOM-79 decreased the upstroke velocity (Vmax) and plateau potential while slightly increased the duration of action potential (APD). Consistent with the decreased Vmax and plateau potential, the peak amplitude of Na+ current (INa) and Ca2+ current (ICa,L) were decreased by KIOM-79. KIOM-79 showed dual effects on hERG K+ current; increase of depolarization phase current (Idepol) and decreased tail current at repolarization phase (Itail). The increase of APD was suspected due to the decreased Itail. In computer simulation, the change of cardiac action potential could be well simulated based on the effects of KIOM-79 on various membrane currents. As a whole, the influence of KIOM-79 on cardiac ion channels are minor at concentrations effective for the diabetic models (0.1-10 microg/mL). The results suggest safety in terms of the risk of cardiac arrhythmia. Also, our study demonstrates the usefulness of the cardiac computer simulation in screening drug-induced long-QT syndrome.

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.

Quantitative connexin mRNA detection in posterior nodal extension of adult rat heart / 南方医科大学学报

<p><b>OBJECTIVE</b>To quantitatively detect the expression of connexins (Cx) mRNA in the posterior nodal extension (PNE) of adult rat heart and understand the relationship between Cx expression and atrial ventricular nodal reentrant tachycardia (AVNRT).</p><p><b>METHODS</b>PNE was separated from adult rat heart by means of laser microdissection (LCM), and the cells were also isolated from the atrioventricular node (AVN), sinoatrial node (SAN), Purkinje fiber (PF), right atrium (RA) and right ventricle (RV), to serve as the controls. The Cx mRNA level was detected in these cells with quantitative real-time PCR (QRT-PCR).</p><p><b>RESULTS</b>The cells were successfully isolated from the PNE and other regions of adult rat heart, where heterogeneous expression of the 3 Cx isoforms (Cx43, Cx45, and Cx40) were observed. Cx45 mRNA showed higher expression in the PNE than in the working myocardium, whereas Cx43 mRNA level was about 25 times higher (P<0.05) in the working myocardium and 18 times higher (P<0.05) in the PF than in the PNE. In the PF, Cx40 mRNA level was proximately 6.8 times (P<0.01) as much as that in the PNE. Cx expression in the PNE was, however, similar to that in the SAN and AVN.</p><p><b>CONCLUSION</b>Cx mRNAs exhibit heterogeneous expression in the PNE to allow the formation of the slow pathway. In addition, Cx expression in the PNE is very different from that in the adjacent myocardium, resulting in conduction discontinuity at the cellular junction, where, on certain occasion, unidirectional block may occur to cause AVNRT.</p>

A case of hyperkalemia-induced complete atrioventricular block with a narrow QRS complex / 대한내과학회지

Hyperkalemia induces wide spectrum of electrocardiographic abnormalities on its severity. In general, hyperkalemia produces a gradual depression of the excitability, conduction velocity of the specialized pacemaker cells and conducting tissues throughout the heart. High serum potassium levels are thought to impair the conduction in the Purkinje fibers and ventricles more than in the AV node, although complete AV block can occur. So, hyperkalemia-induced complete AV block without prolongation of the QRS complex is a rare condition. We report a case of complete AV block without QRS complex widening in patient with hyperkalemia. To our knowledge, this is the first reported case in Korea.

Effects of Cisapride on Action Potential Duration and on ATP-Sensitive K Channel in Guinea Pig Ventricular Muscles

PURPOSE: Cisapride(Prepulsid(R)) has been recently associated with long QT syndrome. It has been reported to cause Torsades de Pointes and induce early afterdepolarization in rabbit Purkinje fibers. We investigated the electrophysiological effects of cisapride on cardiac action potential duration and ATP-sensitive K channel in papillary muscles. METHODS: Cardiac action potentials in guinea pig papillary muscle were recorded with microelectrodes by electrical stimulation. The concentration and time dependent effects of cisapride on the ventricular muscle were studied. The effects of cisapride were evaluated in the presence of potassium channel blockers. The effect of cisapride in isolated single ventricular myocyte was also evaluated. RESULTS: Cisapride lengthened the action potential duration(APD). The lengthening depended on doses of cisapride and exposure time. The APD prolongation was attenuated by glibenclamide pretreatment, not tetraethylammonium. Cisapride inhibits pinacidil-induced KATP channel activity dose dependently in cell-attached membrane patch. APD prolongation in Purkinje fibers was more prominent than these in the ventricular muscle. CONCLUSION: These results suggest that cisapride lengthens APD in ventricular muscle and that cisapride-induced APD prolongation may be partially linked with KATP channel inhibition.

Effects of Bupivacaine on the Membrane Potential and Intracellular Na

BACKGROUND: Bupivacaine is a potent, and commonly used, long acting local anesthetic. If accidentally injected into the systemic circulation, bupivacaine can cause lethal dysrhythmias and circulatory collapse. Attempts to treat bupivacaine induced cardiac toxicity have been varied and controversial, and they have not been very successful. The aim of this study was to investigate the electrophysiologic effects of bupivacaine in Purkinje fibers. METHODS: Effects of bupivacaine on the membrane potential were studied in 12 isolated canine Purkinje fibers. Purkinje fibers from ventricle were dissected and mounted in a tissue chamber perfused with Tyrode's solution. Transmembrane potentials recorded through glass microelectrodes filled with 3M KCI in the beating or quiescent Purkinje fibers during infusions of bupivacaine at concentratons of 3*10/-7M,10/-6M, 3*10/-6M,10/-5M, and 3*10/-5M. RESULTS: Bupivacaine reduced action potential druation in a dose-dependent manner. Bupivacaine produced a decrease in intracelullar sodium ion activity in driven(1Hz) and quiescent canine Purkinje fibers. Bupivacaine-induced hyperpolarizaton of diastolic membrane potential in quiescent Purkinje fibers was dose dependent, and the hyperpolarization by bupivacaine was attenuated by depolarization induced by high potassium extracellular concentration in part. CONCLUSIONS: These results suggest that bupivacaine decreases the fast inward sodium current, and inhibits pacemaker current in canine Purkinje fibers.

Role of alpha-Adrenergic Receptors in the Development of Delayed Afterdepolarization

BACKGROUND: To investigate the role of alpha-adrenergic receptors in the development of delayed afterdepolarization, the effect of alpha-adrenoceptor stimulation and blockade on ouabain induced delayed afterdepolarization(DDAD) was examined in rabbit heart Purkinje fibers. METHODS: Purkinje fibers, taken from adult rabbit(1.8 - 2.0kg) heart anesthetized with penobarbital, were mounted in a Luicite chamber and superfused with Tyrode's solution. The transmembrane potentials were measured by the conventional microelectrode technique while the fibers were being stimulated with rectangular pulses of 50% above threshold voltage. The delayed afterdepolarizations were induced by overdrive excitation in the presence of ouabain. RESULTS: Delayed afterdepolarizations were not observed during superfusion of the control Tyrode's solution containing propranolol(5x10(-7)M). However, the addition of ouabain in the presence of propranolol elicited DADs which were dose-, time- and drive cycle length- dependent. Phenylephrine(PE ; 10(-7)M), and alpha-adrenoceptor agonist, potentiated the ouabain-induced DAD during the initial superfusion(for 10 or 20 min) of the test Tyrode's solution. However, it was followed by attenuating-effects after a superfusion time of 50 to 60 min. Both effects showed ouabain dose-dependence. Ouabain(2x10(-7)M), in the presence of propranolol, depolarized the maximum diastolic potential and shortened the action potential duration, and the addition of PE(10(-7)M) did not affect the characteristics of action potential except a decrease in velocity of phase 0 depolarization. Prazosin, an alpha1-adrenoceptor antagonist, inhibited the PE's enhancing effects of ouabaininduced DDAD at 20 min superfusion, but did not affect the attenuating-effects of PE at 60 min superfusion. On the other hand, yohimbine, an alpha2-adrenoceptor antagonist, did not affect the PE's DAD potentiating-effects at 20 min superfusion, but inhibited the attenunating-effects of PE at 60 min superfusion. CONCLUSION: It is inferred that alpha-adrenergic stimulation induce delayed afterdepolarization and triggered activity in the rabbits, being responsible for the arrhythmia development, and the effects are mainly due to the action of alpha1-subtpe adrenoceptor stimulation.

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 Hyperosmolar Solution on the Twitch Force, Membrane Potential, and Intracellular Sodium Activity in Purkinje Fibers and Ventricular Muscles

BACKGROUND: Hypertonic solutions are using in emergency patients including refractory shock. The effects of the hyperosmotic solutions for the cardiac contractile effect has remained unclear. To study the mechanism of increase in twitch force by hypertonic solution, memberane potential, intracellular sodium activities(aNia), and twitch force were measured simultaneously in 1 Hz-driven canine Purkinje fibers and guinea pig papillary muscles. METHODS: To increase osmolarity, 20, 40, and 80 mOsm glucose, NaCl or mannitol was added to normal Tyrode solution. We used the conventional and Na(+)-selective microelectrodes, to study the membrane potential and intracellular sodium activity. Changes in twitch force were evaluated also by tension tranducer. RESULTS: 1) Hyperosmolar glucose or NaCl added to normal Tyrode solution produced membrane pontential hyperpolarization, increase in aNia, and increase in twitch force in dog Purkinje fibers. Increase in twitch force was related to decrease in the ratio of aNia to extracellular sodium activity(aNoa). NaCl-inducedd aNia increase was not blocked by 10(-5)M tetrodotoxin, a fast sodium channel blocker. 2) Hyperosmolar glucose or mannitol added to normal Tyrode solution produced membrane potential hyperpolarization, increase in aNia, and increase in twitch force in guinea pig papillary muscles. However, the addition of hyperosmolar NaCl did not affect on membrane potential, but produced increase in aNia, and decrease in twitch force. 3) Prolonging effect of hyperosmolar glucose on duration of action potential was smaller than that of NaCl or mannitol in Purkinje fibers and papillary muscles. 4) Increase in twich force produced by ECF Na+reduction or by hyperosmotic solution was reated to decrase in the aNia ratio. 5) Relationship curve between increase in twitch force and aNoa/aNia ratio in hyperosmolr solution was less steeper than that in ECF Na(+)-reduced solution. CONCLUSION: The above results suggested that hyperosmolar solution-induced twitch force change was related to aNoa/aNia ratio change which influenced intracellular calcium activity via Na(+)-Ca(2+)exchange.