Optical Mapping of the Human Atrioventricular Junction

Hucker, William J.; Fedorov, Vadim V.; Foyil, Kelley V.; Moazami, Nader; Efimov, Igor R.

doi:10.1161/circulationaha.107.733147

Cited by 45 publications

(47 citation statements)

References 5 publications

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“…6C. The baseline His conduction velocities measured in LMC and LQT1 rabbits are comparable to His CV described in humans (0.8 m/s) (19). The baseline His CV tended to be slower in LQT2 that in LQT1 rabbits, indicating that a baseline difference may contribute to the pronounced genotype difference in His conduction (HV, His-Wenckebach CL, and His-ERP) between LQT2 and LQT1 rabbits under isoflurane anesthesia.…”

Section: Discussionsupporting

confidence: 63%

“…The field of view was set to 4 ϫ 4 mm (40 ϫ 40 m spatial resolution) to locate and record signals from the AV junction to obtain high-resolution His signal recordings and map His activation (using a 25-mm f0.95 Navitar video lens). As described (7,19,20), the fluorescence signal recorded from the single pixel at the AV junction is the sum of multiple cells in the region, including cells from deeper layers (depth of the field of view 200 m). At the proximal junction, a summation of atrial, AV nodal, and proximal His signals is seen, whereas at the distal AV junction, a summation of His and ventricular signals is seen.…”

Section: Methodsmentioning

confidence: 99%

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Electrophysiological studies of transgenic long QT type 1 and type 2 rabbits reveal genotype-specific differences in ventricular refractoriness and His conduction

Odening

Kirk

Brunner

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

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studies of transgenic long QT type 1 and type 2 rabbits reveal genotype-specific differences in ventricular refractoriness and His conduction. Am J Physiol Heart Circ Physiol 299: H643-H655, 2010. First published June 25, 2010; doi:10.1152/ajpheart.00074.2010.-We have generated transgenic rabbits lacking cardiac slow delayed-rectifier K ϩ current [IKs; long QT syndrome type 1 (LQT1)] or rapidly activating delayedrectifier K ϩ current [IKr; long QT syndrome type 2 (LQT2)]. Rabbits with either genotype have prolonged action potential duration and QT intervals; however, only LQT2 rabbits develop atrioventricular (AV) blocks and polymorphic ventricular tachycardia. We therefore sought to characterize the genotype-specific differences in AV conduction and ventricular refractoriness in LQT1 and LQT2 rabbits. We carried out in vivo electrophysiological studies in LQT1, LQT2, and littermate control (LMC) rabbits at baseline, during isoproterenol infusion, and after a bolus of dofetilide and ex vivo optical mapping studies of the AV node/ His-region at baseline and during dofetilide perfusion. Under isoflurane anesthesia, LQT2 rabbits developed infra-His blocks, decremental His conduction, and prolongation of the Wenckebach cycle length. In LQT1 rabbits, dofetilide altered the His morphology and slowed His conduction, resulting in intra-His block, and additionally prolonged the ventricular refractoriness, leading to pseudo-AV block. The ventricular effective refractory period (VERP) in right ventricular apex and base was significantly longer in LQT2 than LQT1 (P Ͻ 0.05) or LMC (P Ͻ 0.01), with a greater VERP dispersion in LQT2 than LQT1 rabbits. Isoproterenol reduced the VERP dispersion in LQT2 rabbits by shortening the VERP in the base more than in the apex but had no effect on VERP in LQT1. EPS and optical mapping experiments demonstrated genotype-specific differences in AV conduction and ventricular refractoriness. The occurrence of infra-His blocks in LQT2 rabbits under isoflurane and intra-His block in LQT1 rabbits after dofetilide suggest differential regional sensitivities of the rabbit His-Purkinje system to drugs blocking IKr and IKs.long QT syndrome; His-Purkinje conduction; rapidly activating delayed-rectifier potassium current; slow delayed-rectifier potassium current; transgenic rabbit model; pharmacogenomics; ventricular effective refractory period dispersion; in vivo electrophysiological study THE INHERITED LONG-QT SYNDROME (LQTS) is a genetically heterogeneous arrhythmic disease characterized by impaired cardiac repolarization leading to QT prolongation, polymorphic ventricular tachycardia (pVT), and sudden cardiac death (SCD) (reviewed in Ref. 34). The most common forms of LQTS, type 1 and type 2 (LQT1 and LQT2), account for Ͼ90% of the genotyped cases and are due to loss-of-function mutations in KvLQT1 [␣-subunit of slow delayed-rectifier K ϩ current (I Ks )] (11) or HERG [␣-subunit of rapidly activating delayed-rectifier K ϩ current (I Kr )] (9), respectively. The known triggers for pVTs in LQTS vary f...

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Section: Discussionsupporting

confidence: 63%

Section: Methodsmentioning

confidence: 99%

Electrophysiological studies of transgenic long QT type 1 and type 2 rabbits reveal genotype-specific differences in ventricular refractoriness and His conduction

Odening

Kirk

Brunner

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

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“…Relatively normal hearts can be sometimes obtained from organ donors whose heart has been rejected for transplantation because of factors such as age or modest coronary artery disease. The human preparations described in the reports included whole Langendorff-perfused hearts [21,22], transmural wedges of left ventricular tissue perfused through a cannulated coronary artery branch [23], perfused isolated atrioventricular (AV) junction [24] and superfused human atria [25].…”

Section: Mapping the Human Heartmentioning

confidence: 99%

Optical Mapping: Its Impact on Understanding Arrhythmia Mechanisms

2012

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“…As previously stated, mathematical models presented in this study have been based in experimental recordings from rabbits preparations. Recently the His electrogram alternance phenomenon was demonstrated in an explanted human heart [93]. This, together with new improvements on intracardiac recording equipment by means of novel electroanatomical navigation systems (i.e.…”

Section: Guides For Future Workmentioning

confidence: 95%

“…In addition, the complex morphological structures that anatomically and functionally form the atrioventricular tissues have not been included yet in mathematical models due to the difficulties associated with their analysis and characterization by means of current histological and electrophysiological recording tools. However, recently, great advances have been done in the structural [91,92,93] and electrical [94] characterization of these structures at least in a rabbit model.…”

Section: Models Of Av Node Cells and Anatomical Structuresmentioning

confidence: 99%

Characterization and Modeling of Atrioventricular Conduction during Atrial Fibrillation

Climent¹,

Andreu²

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AgradecimientosLa consecución de la presente tesis hubiese sido completamente imposible sin la colaboración de numerosas personas que me han ayudado, enseñado y apoyado durante estos años. Quiero empezar agradeciendo el apoyo recibido por todos los integrantes del grupo de Bioingeniería del instituto ITACA de la Universidad Politécnica de Valencia desde que empecé a colaborar con ellos en 2005. De todos los que durante este tiempo han pasado por el laboratorio he aprendido muchísimo y tengo un más que grato recuerdo: Jose Luis Espí, José Laparra, Jose Antonio Belloch, Laura Maestro, Vicky Donis, Cinta Barber, Amparo Pomar, María Mozo, Lola Guerrero, Lydia Dux, Martina Srutova, Pietro Bonizzi, Lorena Rausell, Jesús Vila y Xavier Ibáñez. Y por supuesto quiero mandar un caluroso agradecimiento a todos con los que sigo trabajando día a día y de los que cada día aprendo nuevas cosas: Jorge Pedrón, Alejandro Liberos, Eduard Roses, Toni Guill, Alvaro Tormos, José Antonio Pérez, Toni Cebrián, Paco Castells, Conrado Calvo, Amador Ayala, María Vinaches, Cristina Rojas, Adolfo Fonseca, Jesús Escrivá y Miguel Rodrigo. Comentario a parte merece José Millet del cual he aprendido innombrables cosas y cuyo espíritu entusiasta y su capacidad de encajar los problemas con tranquilidad son virtudes que querría tener la capacidad de imitar y que me acompañasen durante el resto de mi carrera.Además del apoyo de todos los compañeros del laboratorio, la realización de las diversas estancias de investigación ha sido imprescindible para que esta tesis haya llegado a buen término. Junto con el Dr. Andreas Bollmann entré en el mundo de la ciencia, deél aprendí algunas de las lecciones más valiosas entre las que quiero destacar elímpetu por colaborar y aprender siempre con los mejores estuviesen en el laboratorio de al lado o a 5000km. Este afán por conseguir enriquecer nuestras investigaciones con el apoyo de algunos de los más reputados expertos del mundo me ha llevado a Milán junto con a la Dra. Valentina Corino y al Dr. Luca Mainardi, a Suecia con los Drs. Martin Stridth y Leif Srnmo, a Cleveland junto con los Drs. Youhua Zhang y Todor Mazgalev y a Michigan junto con los Drs. Omer Berenfeld y José Jalife. Cada una de esas estancias me ha enriquecido no sólo como investigador sino como persona. Poder colaborar con investigadores tan reputados a la vez que grandes personas ha sido un regalo que es difícil de describir en unas pocas palabras pero que viajará i ii AGRADECIMIENTOS conmigo el resto de mi vida. Junto con las colaboraciones internacionales, en mi por ahora corta carrera como investigador he tenido la suerte de trabajar con grandes investigadores españoles entre los que quiero destacar a los Drs. Felipe Atienza, Aurelio Quesada y Javier Chorro por confiar en nosotros pese a nuestra juventud, ayudarnos con nuestras limitaciones y descubrirnos la parte más humana de la práctica clínica y la investigación.En el futuro, ojalá tenga la suerte de poder seguir contando con la colaboración de todos estos magníficos científicos y espero ...

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Optical Mapping of the Human Atrioventricular Junction

Cited by 45 publications

References 5 publications

Electrophysiological studies of transgenic long QT type 1 and type 2 rabbits reveal genotype-specific differences in ventricular refractoriness and His conduction

Electrophysiological studies of transgenic long QT type 1 and type 2 rabbits reveal genotype-specific differences in ventricular refractoriness and His conduction

Optical Mapping: Its Impact on Understanding Arrhythmia Mechanisms

Characterization and Modeling of Atrioventricular Conduction during Atrial Fibrillation

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