RESUMEN
BACKGROUND: Local impedance (LI) drop measured with microfidelity electrodes embedded in the tip of an ablation catheter accurately reflects tissue heating during radiofrequency (RF) ablation. Previous studies found 15-30 Ω LI drops created successful lesions, while more than 40 Ω drops were associated with steam pops. The objective of this study was to evaluate the safety and efficacy of LI-guided ablation using standard (30 W) and high-power (50 W) in a preclinical model. METHODS: RF lesions were created in explanted swine hearts (n = 6) to assess the feasibility of LI-guided ablation by targeting 10, 20, or 30 Ω (n = 20/group) drops. Subsequently, LI-guided ablation was evaluated in a chronic animal model (n = 8 Canines, 25-29 kg, 30/50 W). During the index procedure point-by-point intercaval line ablation and left inferior pulmonary vein (PV) isolation were performed. RF duration was at the operators' discretion but discontinued early if a 15-30 Ω drop was achieved. Operators attempted to avoid LI drops of more than 40 Ω. At 1-month, durable conduction block was evaluated with electroanatomic mapping followed by necropsy and histopathology. RESULTS: In explanted tissue, terminating ablation at 10, 20, or 30 Ω LI drops created statistically larger lesions (p < .05; 1.8 [1.6-2.4] mm, 3.3 [3.0-3.7] mm; 4.9 [4.3-5.5] mm). LI-guided high-power ablation in vivo significantly reduced RF duration per application compared to standard-power (p < .05; intercaval: 8.9 ± 5.2 vs. 18.1 ± 11.0 s, PV: 9.6 ± 5.4 vs. 23.2 ± 10.3 s). LI drops of 15-40 Ω were more readily achievable for high-power (90.1%, 318/353) than standard-power (71.7%, 243/339). All intercaval lines and PV isolations were durable (16/16) at 1-month. Necropsy revealed no major collateral injury to the pericardium, phrenic nerve, esophagus, or lungs. There was no pericardial effusion, stroke, tamponade, or PV stenosis. Vagal nerve injury was found in two 30 W animals after using 19.7 ± 13.9 and 19.5 ± 11.8 s RF applications. CONCLUSION: LI-guided ablation was found to be safe and efficacious in a chronic animal model. High-power ablation more readily achieved more than 15 Ω drops, reduced RF duration compared with standard-power, and had no major RF collateral injury.
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Ablación por Catéter , Venas Pulmonares , Animales , Arritmias Cardíacas , Ablación por Catéter/efectos adversos , Modelos Animales de Enfermedad , Perros , Impedancia Eléctrica , Venas Pulmonares/cirugía , PorcinosRESUMEN
AIMS: Radiofrequency ablation creates irreversible cardiac damage through resistive heating and this temperature change results in a generator impedance drop. Evaluation of a novel local impedance (LI) technology measured exclusively at the tip of the ablation catheter found that larger LI drops were indicative of more effective lesion formation. We aimed to evaluate whether LI drop is associated with conduction block in patients with paroxysmal atrial fibrillation (AF) undergoing pulmonary vein isolation (PVI). METHODS AND RESULTS: Sixty patients underwent LI-blinded de novo PVI using a point-by-point ablation workflow. Pulmonary vein rings were divided into 16 anatomical segments. After a 20-min waiting period, gaps were identified on electroanatomic maps. Median LI drop within segments with inter-lesion distance ≤6 mm was calculated offline. The diagnostic accuracy of LI drop for predicting segment block was assessed using receiver operating characteristic analysis. For segments with inter-lesion distance ≤6 mm, acutely blocked segments had a significantly larger LI drop [19.8 (14.1-27.1) Ω] compared with segments with gaps [10.6 (7.8-14.7) Ω, P < 0.001). In view of left atrial wall thickness differences, the association between LI drop and block was further evaluated for anterior/roof and posterior/inferior segments. The optimal LI cut-off value for anterior/roof segments was 16.1 Ω (positive predictive value for block: 96.3%) and for posterior/inferior segments was 12.3 Ω (positive predictive value for block: 98.1%) where inter-lesion distances were ≤6 mm. CONCLUSION: The magnitude of LI drop was predictive of acute PVI segment conduction block in patients with paroxysmal AF. The thinner posterior wall required smaller LI drops for block compared with the thicker anterior wall.
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Fibrilación Atrial , Ablación por Catéter , Venas Pulmonares , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/cirugía , Catéteres , Impedancia Eléctrica , Humanos , Venas Pulmonares/cirugía , Resultado del TratamientoRESUMEN
AIMS: Cryoballoon pulmonary vein isolation (PVI) is a safe and effective treatment for atrial fibrillation (AF). Current limitations include incomplete vein occlusion due to balloon rigidity and inconsistent electrogram recording, which impairs identification of isolation. We aimed to evaluate the acute safety and performance of a novel cryoballoon system. METHODS AND RESULTS: The system includes a steerable sheath, mapping catheter, and a balloon that maintains uniform inflation pressure and size following initiation of ablation. Protocol-directed cryoablation was delivered for 180 s for isolation documented in ≤60 s, otherwise freeze duration was 240 s. Primary endpoints were acute safety and vein isolation. Pulmonary vein isolation was confirmed at ≥30 min post-isolation. Data were compared across vein locations. Thirty patients with paroxysmal AF were enrolled at two centres and underwent PVI. Pulmonary vein isolation was achieved with cryoablation only in 100% of veins (120/120). Nadir temperature was -53.1 ± 5.3°C. The number of applications to achieve PVI was 1.4 ± 0.4 per vein. Of the 120 veins, 89 were isolated with a single cryothermal application (10/30 patients required only 4 total cryoablations). There were no procedural- or device-related serious adverse events at 30 days post-procedure. A subset (24/30) of patients was followed for 1-year and 71% (17/24) remained free of atrial arrhythmias. Six patients with arrhythmia recurrence were remapped and three had durable PVI for all four veins. CONCLUSION: In this first human experience, the novel cryoballoon platform was safe, efficacious, and demonstrated a high proportion of successful single ablation isolation.
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Fibrilación Atrial , Ablación por Catéter , Criocirugía , Venas Pulmonares , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/cirugía , Criocirugía/efectos adversos , Humanos , Venas Pulmonares/cirugía , Recurrencia , Resultado del TratamientoRESUMEN
The copy number of membrane proteins at the cell surface is tightly regulated. Many ion channels and receptors present retrieval motifs to COPI vesicle coats and are retained in the early secretory pathway. In some cases, the interaction with COPI is prevented by binding to 14-3-3 proteins. However, the functional significance of this antagonism between COPI and 14-3-3 in terminally differentiated cells is unknown. Here, we show that ATP-sensitive K(+) (KATP) channels, which are composed of Kir6.2 and SUR1 subunits, are stalled in the Golgi complex of ventricular, but not atrial, cardiomyocytes. Upon sustained ß-adrenergic stimulation, which leads to activation of protein kinase A (PKA), SUR1-containing channels reach the plasma membrane of ventricular cells. We show that PKA-dependent phosphorylation of the C-terminus of Kir6.2 decreases binding to COPI and, thereby, silences the arginine-based retrieval signal. Thus, activation of the sympathetic nervous system releases this population of KATP channels from storage in the Golgi and, hence, might facilitate the adaptive response to metabolic challenges.
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Canales KATP/metabolismo , Receptores de Sulfonilureas/metabolismo , Proteínas 14-3-3/metabolismo , Animales , Western Blotting , Células Cultivadas , Cromatografía de Afinidad , Electrofisiología , Técnica del Anticuerpo Fluorescente Indirecta , Inmunoprecipitación , Masculino , Ratones , Ratones Noqueados , Canales de Potasio de Rectificación Interna/metabolismo , Transporte de Proteínas/fisiologíaRESUMEN
The ventricular human myocyte is spatially organized for optimal ATP and Ca(2+) delivery to sarcomeric myosin and ionic pumps during every excitation-contraction cycle. Comprehension of three-dimensional geometry of the tightly packed ultrastructure has been derived from discontinuous two-dimensional images, but has never been precisely reconstructed or analyzed in human myocardium. Using a focused ion beam scanning electron microscope, we created nanoscale resolution serial images to quantify the three-dimensional ultrastructure of a human left ventricular myocyte. Transverse tubules (t-tubule), lipid droplets, A-bands, and mitochondria occupy 1.8, 1.9, 10.8, and 27.9% of the myocyte volume, respectively. The complex t-tubule system has a small tortuosity (1.04±0.01), and is composed of long transverse segments with diameters of 317±24nm and short branches. Our data indicates that lipid droplets located well beneath the sarcolemma are proximal to t-tubules, where 59% (13 of 22) of lipid droplet centroids are within 0.50µm of a t-tubule. This spatial association could have an important implication in the development and treatment of heart failure because it connects two independently known pathophysiological alterations, a substrate switch from fatty acids to glucose and t-tubular derangement.
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Ventrículos Cardíacos/ultraestructura , Células Musculares/ultraestructura , Miocardio/ultraestructura , Miocitos Cardíacos/ultraestructura , Adenosina Trifosfato/metabolismo , Calcio/metabolismo , Ventrículos Cardíacos/metabolismo , Humanos , Imagenología Tridimensional , Gotas Lipídicas/metabolismo , Gotas Lipídicas/ultraestructura , Microscopía Electrónica de Rastreo , Células Musculares/metabolismo , Miocitos Cardíacos/metabolismo , Sarcolema/ultraestructuraRESUMEN
Instability of the inner mitochondrial membrane potential (ΔΨm) has been implicated in electrical dysfunction, including arrhythmogenesis during ischemia-reperfusion. Monitoring ΔΨm has led to conflicting results, where depolarization has been reported as sporadic and as a propagating wave. The present study was designed to resolve the aforementioned difference and determine the unknown relationship between ΔΨm and electrophysiology. We developed a novel imaging modality for simultaneous optical mapping of ΔΨm and transmembrane potential (Vm). Optical mapping was performed using potentiometric dyes on preparations from 4 mouse hearts, 14 rabbit hearts, and 7 human hearts. Our data showed that during ischemia, ΔΨm depolarization is sporadic and changes asynchronously with electrophysiological changes. Spatially, ΔΨm depolarization was associated with action potential duration shortening but not conduction slowing. Analysis of focal activity indicated that ΔΨm is not different within the myocardium where the focus originates compared with normal ventricular tissue. Overall, our data suggest that during ischemia, mitochondria maintain their function at the expense of sarcolemmal electrophysiology, but ΔΨm depolarization does not have a direct association to ischemia-induced arrhythmias.
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Potenciales de Acción , Potencial de la Membrana Mitocondrial , Isquemia Miocárdica/metabolismo , Animales , Humanos , Ratones , Mitocondrias/metabolismo , Mitocondrias/fisiología , Isquemia Miocárdica/fisiopatología , Imagen Óptica/métodos , ConejosRESUMEN
Cardiomyopathy is associated with cardiac Na(+) channel downregulation that may contribute to arrhythmias. Previously, we have shown that elevated intracellular NADH causes a decrease in cardiac Na(+) current (I(Na)) signaled by an increase in mitochondrial reactive oxygen species (ROS). In this study, we tested whether the NADH-mitochondria ROS pathway was involved in the reduction of I(Na) in a nonischemic cardiomyopathic model and correlated the findings with myopathic human hearts. Nonischemic cardiomyopathy was induced in C57BL/6 mice by hypertension after unilateral nephrectomy, deoxycorticosterone acetate (DOCA) pellet implantation, and salt water substitution. Sham operated mice were used as controls. After six weeks, heart tissue and ventricular myocytes isolated from mice were utilized for whole cell patch clamp recording, NADH/NAD(+) level measurements, and mitochondrial ROS monitoring with confocal microscopy. Human explanted hearts were studied using optical mapping. Compared to the sham mice, the arterial blood pressure was higher, the left ventricular volume was significantly enlarged (104.7±3.9 vs. 87.9±6.1 µL, P<0.05), and the ejection fraction was reduced (37.1±1.8% vs. 49.4±3.7%, P<0.05) in DOCA mice. Both the whole cell and cytosolic NADH level were increased (279±70% and 123±2% of sham, respectively, P<0.01), I(Na) was decreased (60±10% of sham, P<0.01), and mitochondrial ROS overproduction was observed (2.9±0.3-fold of sham, P<0.01) in heart tissue and myocytes of myopathic mice vs. sham. Treatment of myocytes with NAD(+) (500 µM), mitoTEMPO (10 µM), chelerythrine (50 µM), or forskolin (5 µM) restored I(Na) back to the level of sham. Injection of NAD(+) (100mg/kg) or mitoTEMPO (0.7 mg/kg) twice (at 24h and 1h before myocyte isolation) to animals also restored I(Na). All treatments simultaneously reduced mitochondrial ROS levels to that of controls. CD38 was found to transduce the extracellular NAD(+) signal. Correlating with the mouse model, failing human hearts showed a reduction in conduction velocity that improved with NAD(+). Nonischemic cardiomyopathy was associated with elevated NADH level, PKC activation, mitochondrial ROS overproduction, and a concomitant decrease in I(Na). Reducing mitochondrial ROS by application of NAD(+), mitoTEMPO, PKC inhibitors, or PKA activators, restored I(Na). NAD(+) improved conduction velocity in human myopathic hearts.
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Cardiomiopatías/metabolismo , Mitocondrias Cardíacas/fisiología , Canal de Sodio Activado por Voltaje NAV1.5/metabolismo , ADP-Ribosil Ciclasa 1/metabolismo , Potenciales de Acción/efectos de los fármacos , Animales , Benzofenantridinas/farmacología , Colforsina/farmacología , Regulación hacia Abajo , Sistema de Conducción Cardíaco/efectos de los fármacos , Sistema de Conducción Cardíaco/fisiopatología , Humanos , Técnicas In Vitro , Glicoproteínas de Membrana/metabolismo , Potenciales de la Membrana/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/fisiología , NAD/metabolismo , NAD/farmacología , Canal de Sodio Activado por Voltaje NAV1.5/genética , Compuestos Organofosforados/farmacología , Estrés Oxidativo , Técnicas de Placa-Clamp , Piperidinas/farmacología , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Sarcolemmal CD36 facilitates myocardial fatty acid (FA) uptake, which is markedly reduced in CD36-deficient rodents and humans. CD36 also mediates signal transduction events involving a number of cellular pathways. In taste cells and macrophages, CD36 signaling was recently shown to regulate store-responsive Ca(2+) flux and activation of Ca(2+)-dependent phospholipases A(2) that cycle polyunsaturated FA into phospholipids. It is unknown whether CD36 deficiency influences myocardial Ca(2+) handling and phospholipid metabolism, which could compromise the heart, typically during stresses. Myocardial function was examined in fed or fasted (18-22 h) CD36(-/-) and WT mice. Echocardiography and telemetry identified conduction anomalies that were associated with the incidence of sudden death in fasted CD36(-/-) mice. No anomalies or death occurred in WT mice during fasting. Optical imaging of perfused hearts from fasted CD36(-/-) mice documented prolongation of Ca(2+) transients. Consistent with this, knockdown of CD36 in cardiomyocytes delayed clearance of cytosolic Ca(2+). Hearts of CD36(-/-) mice (fed or fasted) had 3-fold higher SERCA2a and 40% lower phospholamban levels. Phospholamban phosphorylation by protein kinase A (PKA) was enhanced after fasting reflecting increased PKA activity and cAMP levels in CD36(-/-) hearts. Abnormal Ca(2+) homeostasis in the CD36(-/-) myocardium associated with increased lysophospholipid content and a higher proportion of 22:6 FA in phospholipids suggests altered phospholipase A(2) activity and changes in membrane dynamics. The data support the role of CD36 in coordinating Ca(2+) homeostasis and lipid metabolism and the importance of this role during myocardial adaptation to fasting. Potential relevance of the findings to CD36-deficient humans would need to be determined.
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Antígenos CD36/biosíntesis , Calcio/metabolismo , Miocardio/metabolismo , Fosfolípidos/metabolismo , Alimentación Animal , Animales , AMP Cíclico/metabolismo , Electrocardiografía/métodos , Ácidos Grasos Insaturados/metabolismo , Homeostasis , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Fosfolípidos/química , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico/metabolismo , Factores de TiempoRESUMEN
Since its inception in 19th-century Germany, the physiology laboratory has been a complex and expensive research enterprise involving experts in various fields of science and engineering. Physiology research has been critically dependent on cutting-edge technological support of mechanical, electrical, optical, and more recently computer engineers. Evolution of modern experimental equipment is constrained by lack of direct communication between the physiological community and industry producing this equipment. Fortunately, recent advances in open source technologies, including three-dimensional printing, open source hardware and software, present an exciting opportunity to bring the design and development of research instrumentation to the end user, i.e., life scientists. Here we provide an overview on how to develop customized, cost-effective experimental equipment for physiology laboratories.
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Diseño Asistido por Computadora , Corazón/anatomía & histología , Imagenología Tridimensional , Laboratorios , Fisiología/métodos , Impresión/métodos , Animales , Diseño de Equipo , Humanos , Fisiología/instrumentación , Impresión/instrumentación , Especificidad de la EspecieRESUMEN
Optical mapping has become an increasingly important tool to study cardiac electrophysiology in the past 20 years. Multiple methods are used to process and analyze cardiac optical mapping data, and no consensus currently exists regarding the optimum methods. The specific methods chosen to process optical mapping data are important because inappropriate data processing can affect the content of the data and thus alter the conclusions of the studies. Details of the different steps in processing optical imaging data, including image segmentation, spatial filtering, temporal filtering, and baseline drift removal, are provided in this review. We also provide descriptions of the common analyses performed on data obtained from cardiac optical imaging, including activation mapping, action potential duration mapping, repolarization mapping, conduction velocity measurements, and optical action potential upstroke analysis. Optical mapping is often used to study complex arrhythmias, and we also discuss dominant frequency analysis and phase mapping techniques used for the analysis of cardiac fibrillation.
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Potenciales de Acción , Arritmias Cardíacas/diagnóstico , Colorantes Fluorescentes , Sistema de Conducción Cardíaco/fisiopatología , Procesamiento de Señales Asistido por Computador , Imagen de Colorante Sensible al Voltaje/métodos , Algoritmos , Animales , Arritmias Cardíacas/fisiopatología , Humanos , Valor Predictivo de las Pruebas , Factores de TiempoRESUMEN
Thirty-eight patients had assessment of pulmonary vein occlusion with the dielectric mapping system and injection of saline as an alternative to contrast. Contrast injection was required to ascertain pulmonary vein occlusion in 31.6% (12 of 38) of subjects and 17.4% (27 of 155) of veins. No contrast was required in the last 13 subjects. In this single center study, a novel mapping-guided cryoablation approach appeared to minimize the use of contrast in pulmonary vein isolation for the treatment of atrial fibrillation.
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Fibrilación Atrial , Criocirugía , Venas Pulmonares , Enfermedad Veno-Oclusiva Pulmonar , Fibrilación Atrial/cirugía , Criocirugía/efectos adversos , Estudios de Factibilidad , Humanos , Venas Pulmonares/diagnóstico por imagen , Venas Pulmonares/cirugía , Enfermedad Veno-Oclusiva Pulmonar/cirugía , Resultado del TratamientoRESUMEN
OBJECTIVES: This analysis was performed to evaluate the transition of local impedance (LI) drop during pulmonary vein isolation (PVI) to durable block and mature lesion formation based on 3-month mapping procedures. BACKGROUND: A radiofrequency catheter measuring LI has been shown to be effective for performing PVI in patients with paroxysmal atrial fibrillation. Previous analysis has demonstrated LI drop to be predictive of pulmonary vein segment conduction block during an atrial fibrillation ablation procedure. METHODS: Fifty-eight patients who had undergone LI-blinded de novo PVI returned for a 3-month mapping procedure. PVI ablation circles were divided into 16 anatomic segments for classification (durable block or gap), and the median LI drop within segments with an interlesion distance of ≤6 mm was compared. A total of 51 data sets met the criteria for segmental analysis of LI performance. RESULTS: At the 3-month procedure, PV connection was confirmed in at least 1 PV segment in 35 of the included patients. LI drop outperformed generator impedance drop as a predictor of durable conduction block (area under the receiver-operating characteristic curve: 0.79 vs 0.68; P = 0.003). Optimal LI drops were identified by left atrial region (anterior/superior: 16.9 Ω [sensitivity: 69.1%; specificity: 85.0%; positive predictive value for durable conduction block: 97.7%]; posterior/inferior:14.2 Ω [sensitivity: 73.8%; specificity: 78.3%; positive predictive value: 96.9%]). Starting LI before radiofrequency (RF) application was significantly different among healthy, gap, and mature scar tissue and was also a contributing factor to achieving an optimal LI drop (85.2% of RF applications with a starting LI of ≥110 Ω achieved the optimal regional drop or greater). CONCLUSIONS: LI drop is predictive of durable PV segment isolation. Preablation starting LI is associated with the magnitude of LI drop. These findings suggest that a regional approach to RF ablation guided by LI combined with careful interlesion distance control may be beneficial in patients with paroxysmal atrial fibrillation (Electrical Coupling Information From the Rhythmia HDx System and DirectSense Technology in Subjects With Paroxysmal Atrial Fibrillation [LOCALIZE]; NCT03232645).
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Fibrilación Atrial , Ablación por Catéter , Venas Pulmonares , Ablación por Radiofrecuencia , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/cirugía , Impedancia Eléctrica , Bloqueo Cardíaco/cirugía , Humanos , Venas Pulmonares/cirugíaRESUMEN
[Figure: see text].
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Fibrilación Atrial/cirugía , Catéteres Cardíacos , Ablación por Catéter/instrumentación , Sistema de Conducción Cardíaco/fisiopatología , Venas Pulmonares/cirugía , Cirugía Asistida por Computador/métodos , Adulto , Anciano , Fibrilación Atrial/fisiopatología , Diseño de Equipo , Femenino , Fluoroscopía/métodos , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Recurrencia , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Coupling between the ablation catheter and myocardium is critical to resistively heat tissue with radiofrequency ablation. The objective of this study was to evaluate whether a novel local impedance (LI) measurement on an ablation catheter identifies catheter-tissue coupling and is predictive of lesion formation. METHODS AND RESULTS: LI was studied in explanted hearts (n=10 swine) and in vivo (n=10; 50-70 kg swine) using an investigational electroanatomic mapping system that measures impedance from an ablation catheter with mini-electrodes incorporated in the distal electrode (Rhythmia and IntellaNav MiFi OI, Boston Scientific). Explanted tissue was placed in a warmed (37 °C) saline bath mounted on a scale, and LI was measured 15 mm away from tissue to 5 mm of catheter-tissue compression at multiple catheter angles. Lesions were created with 31 and 50 W for 5 to 45 seconds (n=90). During in vivo evaluation of LI, measurements of myocardium (n=90) and blood pool (n=30) were guided by intracardiac ultrasound while operators were blinded to LI data. Lesions were created with 31 and 50 W for 45 seconds in the ventricles (n=72). LI of myocardium (119.7 Ω) was significantly greater than that of blood pool (67.6 Ω; P<0.01). Models that incorporate LI drop (ΔLI) to predict lesion size had better performance than models that incorporate force-time integral (R2=0.75 versus R2=0.54) and generator impedance drop (R2=0.82 versus R2=0.58). Steam pops displayed a significantly higher starting LI and larger ΔLI compared with successful radiofrequency applications (P<0.01). CONCLUSIONS: LI recorded from miniature electrodes provides a valuable measure of catheter-tissue coupling, and ΔLI is predictive of lesion formation during radiofrequency ablation.
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Catéteres Cardíacos , Ablación por Catéter/instrumentación , Ventrículos Cardíacos/patología , Ventrículos Cardíacos/cirugía , Microelectrodos , Miocardio/patología , Animales , Ablación por Catéter/efectos adversos , Impedancia Eléctrica , Diseño de Equipo , Femenino , Masculino , Modelos Animales , Vapor , Sus scrofaRESUMEN
Although the clinical range of interventions for coronary arteries is about 2 to 5 mm, the range of diameters of peripheral vasculature is significantly larger (about 10 mm for human iliac artery). When the vessel diameter is increased, the spacing between excitation electrodes on a conductance sizing device must also increase to accommodate the greater range of vessel diameters. The increase in the excitation electrodes distance, however, causes higher parallel conductance or current losses outside of artery lumen. We have previously shown that the conductance catheter/guidewire excitation electrode distances affects the measurement accuracy for the peripheral artery lumen sizing. Here, we propose a simple solution that varies the detection electrode distances to compensate for parallel conductance losses. Computational models were constructed to simulate the conductance guidewire with various electrodes spacing combinations over a range of peripheral artery lumen diameters and surrounding tissue electrical conductivities. The results demonstrate that the measurement accuracy may be significantly improved by increased detection spacing. Specifically, an optimally configured detection/excitation spacing (i.e., 5-5-5 or an equidistant electrode interval with a detection-to-excitation spacing ratio of 0.3) was shown to accurately predict the lumen diameter (i.e., -10% < error < 10%) over a broad range of peripheral artery dimensions (4 mm < diameter < 10 mm). The computational results were substantiated with both ex-vivo and in-vivo measurements of peripheral arteries. The present results support the accuracy of the conductance technique for measurement of peripheral reference vessel diameter.
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Vasos Sanguíneos/anatomía & histología , Catéteres , Vasos Coronarios/anatomía & histología , Animales , Aterosclerosis , Cateterismo/instrumentación , Simulación por Computador , Conductividad Eléctrica , Electrodos , Diseño de Equipo , Humanos , Arteria Ilíaca , Masculino , Modelos Cardiovasculares , Modelos Teóricos , Enfermedad Arterial Periférica/terapia , Reproducibilidad de los Resultados , PorcinosRESUMEN
AIMS: Percutaneous structural heart therapies, such as mitral value repair, require site-specific transseptal access (TSA). This can be challenging for interventional cardiologists. We describe a TSA catheter (TSAC) that utilises suction for enhanced control and puncture accuracy. Here, we aim to evaluate the safety and efficacy of the device. METHODS AND RESULTS: Ex vivo interatrial septum preparations were dissected from swine (n=8) and diseased human hearts (n=6) to quantify TSAC suction and needle puncture force. TSAC suction was 6.5-fold greater than the opposing needle puncture force, and thus provides sufficient stabilisation for punctures. The safety and efficacy of TSAC was evaluated in a chronic mitral regurgitation swine model (n=10) and compared to a conventional TSA device. MR was induced by disrupting one to three mitral chordae tendineae, and the progression of heart disease was followed for three weeks. During device testing, procedure time and fluoroscopy exposure were not statistically different between devices. TSAC reduced septal displacement from 8.7±0.30 mm to 3.60±0.19 mm (p<0.05) and improved puncture accuracy 1.75-fold. CONCLUSIONS: TSAC provides controlled TSA and improves puncture accuracy, while maintaining procedure time and workflow. These findings provide a strong rationale for a first-in-man study to demonstrate the clinical utility of the device.
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Tabique Interatrial/cirugía , Diseño de Equipo , Tabiques Cardíacos/cirugía , Punciones , Succión , Animales , Cateterismo Cardíaco/instrumentación , Ablación por Catéter/instrumentación , Femenino , Humanos , Masculino , Punciones/métodos , Succión/métodos , PorcinosRESUMEN
AIMS: The duration and morphology of the T wave predict risk for ventricular fibrillation. A transmural gradient in action potential duration (APD) in the ventricular wall has been suggested to underlie the T wave in humans. We hypothesize that the transmural gradient in APD compensates for the normal endocardium-to-epicardium activation sequence and synchronizes repolarization in the human ventricular wall. METHODS AND RESULTS: We made left ventricular wedge preparations from 10 human donor hearts and measured transmural activation and repolarization patterns by optical mapping, while simultaneously recording a pseudo-ECG. We also studied the relation between local timings of repolarization with the T wave in silico. During endocardial pacing (1 Hz), APD was longer at the subendocardium than at the subepicardium (360 ± 17 vs. 317 ± 20 ms, P < 0.05). The transmural activation time was 32 ± 4 ms and resulted in final repolarization of the subepicardium at 349 ± 18 ms. The overall transmural dispersion in repolarization time was smaller than that of APD. During epicardial pacing, the dispersion in repolarization time increased, whereas that of APD remained similar. The morphology of the T wave did not differ between endocardial and epicardial stimulation. Simulations explained the constant T wave morphology without transmural APD gradients. CONCLUSION: The intrinsic transmural difference in APD compensates for the normal cardiac activation sequence, resulting in more homogeneous repolarization of the left ventricular wall. Our data suggest that the transmural repolarization differences do not fully explain the genesis of the T wave.
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Potenciales de Acción , Función Ventricular Izquierda , Adulto , Anciano , Niño , Electrocardiografía , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Advances in material science techniques and pioneering circuit designs have led to the development of electronic membranes that can form intimate contacts with biological tissues. In this review, we present the range of geometries, sensors, and actuators available for custom configurations of electronic membranes in cardiac applications. Additionally, we highlight the desirable mechanics achieved by such devices that allow the circuits and substrates to deform with the beating heart. These devices unlock opportunities to collect continuous data on the electrical, metabolic, and mechanical state of the heart as well as a platform on which to develop high definition therapeutics.
Asunto(s)
Mapeo del Potencial de Superficie Corporal/instrumentación , Desfibriladores Implantables , Electrocardiografía/instrumentación , Electrodos , Membranas Artificiales , Marcapaso Artificial , Materiales Biocompatibles/síntesis química , Módulo de Elasticidad , Diseño de Equipo , Análisis de Falla de EquipoRESUMEN
OBJECTIVES: The aim of this study was to evaluate the role of tyrosine kinase cellular-Src (c-Src) inhibition on connexin43 (Cx43) regulation in a mouse model of myocardial infarction (MI). BACKGROUND: MI is associated with decreased expression of Cx43, the principal gap junction protein responsible for propagating current in ventricles. Activated c-Src has been linked to Cx43 dysregulation. METHODS: MI was induced in 12-week-old mice by coronary artery occlusion. MI mice were treated with c-Src inhibitors (PP1 or AZD0530), PP3 (an inactive analogue of PP1), or saline. Treated hearts were compared to sham mice by echocardiography, optical mapping, telemetry electrocardiographic monitoring, and inducibility studies. Tissues were collected for immunoblotting, quantitative polymerase chain reaction, and immunohistochemistry. RESULTS: Active c-Src was elevated in PP3-treated MI mice compared to sham at the scar border (280%, p = 0.003) and distal ventricle (346%, p = 0.013). PP1 treatment restored active c-Src to sham levels at the scar border (86%, p = 0.95) and distal ventricle (94%, p = 1.0). PP1 raised Cx43 expression by 69% in the scar border (p = 0.048) and by 73% in the distal ventricle (p = 0.043) compared with PP3 mice. PP1-treated mice had restored conduction velocity at the scar border (PP3: 32 cm/s, PP1: 41 cm/s, p < 0.05) and lower arrhythmic inducibility (PP3: 71%, PP1: 35%, p < 0.05) than PP3 mice. PP1 did not change infarct size, electrocardiographic pattern, or cardiac function. AZD0530 treatment demonstrated restoration of Cx43 comparable to PP1. CONCLUSIONS: c-Src inhibition improved Cx43 levels and conduction velocity and lowered arrhythmia inducibility after MI, suggesting a new approach for arrhythmia reduction following MI.