Anatomic Localization and Autonomic Modulation of Atrioventricular Junctional Rhythm in Failing Human Hearts

Fedorov, Vadim V.; Ambrosi, Christina M.; Kostecki, Geran; Hucker, William J.; Glukhov, Alexey V.; Wuskell, Joseph P.; Loew, Leslie M.; Moazami, Nader; Efimov, Igor R.

doi:10.1161/circep.111.962258

Cited by 47 publications

(43 citation statements)

References 42 publications

(56 reference statements)

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“…However, to date, hemicyanine dyes are the most universally used and applicable VSDs available. Indeed, among the most recent new advances enabled by these dyes, there has been recording of deep aberrant activity patterns in human hearts from transplant patients (27,28) and recording V m spikes (∼1 ms) from individual dendritic spines (29)(30)(31).…”

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confidence: 99%

Palette of fluorinated voltage-sensitive hemicyanine dyes

Yan

Acker²,

Zhou

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Optical recording of membrane potential permits spatially resolved measurement of electrical activity in subcellular regions of single cells, which would be inaccessible to electrodes, and imaging of spatiotemporal patterns of action potential propagation in excitable tissues, such as the brain or heart. However, the available voltage-sensitive dyes (VSDs) are not always spectrally compatible with newly available optical technologies for sensing or manipulating the physiological state of a system. Here, we describe a series of 19 fluorinated VSDs based on the hemicyanine class of chromophores. Strategic placement of the fluorine atoms on the chromophores can result in either blue or red shifts in the absorbance and emission spectra. The range of one-photon excitation wavelengths afforded by these new VSDs spans 440-670 nm; the twophoton excitation range is 900-1,340 nm. The emission of each VSD is shifted by at least 100 nm to the red of its one-photon excitation spectrum. The set of VSDs, thus, affords an extended toolkit for optical recording to match a broad range of experimental requirements. We show the sensitivity to voltage and the photostability of the new VSDs in a series of experimental preparations ranging in scale from single dendritic spines to whole heart. Among the advances shown in these applications are simultaneous recording of voltage and calcium in single dendritic spines and optical electrophysiology recordings using two-photon excitation above 1,100 nm.fluorescence | microscopy O ptical recording techniques provide powerful tools for neurobiologists (1) and cardiac physiologists (2) to study detailed patterns of electrical activity over time and space in cells, tissues, and organs. Rational design methods, based on molecular orbital calculations of the dye chromophores and characterization of their binding and orientations in membranes (3-5), were used to engineer dye structures. The general class of dye chromophores called hemicyanine (also referred to as styryl dyes) has emerged from this effort as a good foundation for voltage-sensitive dyes (VSDs), because they exhibit electrochromism. This mechanism, also referred to as the molecular Stark effect, involves the differential interaction of the electric field in the membrane with the ground and excited states of the dye chromophore. Several important hemicyanine dyes were produced over the years, including di-4-ANEPPS (6, 7), di-8-ANEPPS (8), di-2-ANEPEQ (also known as JPW-1114) (9, 10), RH-421 and RH-795 (11), ANNINE-6 and ANNINE-6+ (12, 13), di-3-ANEPPDHQ (14, 15), di-4-ANBDQBS, and di-4-ANBDQPQ (16,17). Because the electrochromic mechanism is a direct interaction of the electric field with the chromophore and does not require any movement of the dye molecule, all of these dyes provide rapid absorbance and fluorescence responses to membrane potential (V m ); they are, therefore, capable of recording action potentials (APs). Other mechanisms can give more sensitive voltage responses in specialized applications (18)(19)(20)(21)(22). Addit...

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mentioning

confidence: 99%

Palette of fluorinated voltage-sensitive hemicyanine dyes

Yan

Acker²,

Zhou

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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156

163

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“…Moreover, we found that both the fast and slow pathways are involved in anterograde and retrograde conduction. 10 …”

Section: Discussionmentioning

confidence: 99%

Circulation: Heart Failure Editors' Picks

Kociol¹

2012

Circ: Heart Failure

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The following are highlights from Circulation: Heart Failure Topic Review. This series will summarize the most important articles, as selected by the editors, that have published in the Circulation portfolio. The objective of this series is to provide our readership with a timely comprehensive selection of important papers that are relevant to the heart failure audience. The studies included in this article represent the most noteworthy research in the areas of heart failure and electrophysiology. (Circ Heart Fail. 2012;5:e56-e64 Summary: Cardiac Arrhythmias and Risk Stratification After Acute Myocardial Infarction (CARISMA) reports on long-term cardiac arrhythmias recorded by an implantable cardiac monitor in patients with left ventricular ejection fraction Յ40% after myocardial infarction. Clinically significant bradyarrhythmias and tachyarrhythmias were documented in a substantial proportion of patients, most of them asymptomatic. A large number of the documented arrhythmias would result in device therapy according to the current guidelines. The most significant arrhythmia was intermittent high-degree atrioventricular block, which was associated with a very high risk of cardiac death. However, the study was observational, and whether the use of implantable cardiac monitors in this population could improve clinical outcome should be tested in larger randomized trials.Conclusions: This is the first study to report on long-term cardiac arrhythmias recorded by an implantable loop recorder in patients with left ventricular ejection fraction Յ40% after myocardial infarction. Clinically significant bradyarrhythmias and tachyarrhythmias were documented in a substantial proportion of patients with depressed left ventricular ejection fraction after acute myocardial infarction. Intermittent high-degree atrioventricular block was associated with a very high risk of cardiac death. 1 Effect of Long-Term Right Ventricular Pacing in Young Adults With Structurally Normal HeartSummary: This study elucidates the long-term effect of right ventricular (RV) pacing on clinical outcomes in patients who underwent pacemaker implantation for symptomatic isolated congenital complete atrioventricular block (ICAVB). Over a mean follow-up of 20 years (longest, 39 years), the observed survival free of new heart failure (HF) after pacemaker implant in the overall ICAVB group was significantly worse than that of the age-and sex-specific Olmsted County, Minnesota, population rates. This difference was, however, attributable to the development of HF and ventricular dysfunction in those who had tested positive for antinuclear antibody (ANA) during adulthood, with no difference between the antibody negative ICAVB patients and the Olmsted County population. The presence of a positive ANA was a strong predictor for the development of HF and death. These results suggest that in young patients without structural heart disease, pacing from the RV position does not appear to have a detrimental effect on heart size or performance. The risk of HF after p...

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“…Optical mapping of the AVN area in six hearts explanted from patients with advanced heart failure demonstrated that in the absence of SA nodal activation, spontaneous pacemaking activity originates in the nodal-His region and/or the proximal His bundle [30]. After earliest activation in the proximal His and compact AVN, the wavefront moved in retrograde fashion through the fast pathway and slow pathway, with earliest atrial activation via the fast pathway.…”

Section: Optical Mapping Of the Human Avnmentioning

confidence: 99%

“…Importantly, it is clear that both the slow and fast pathways permit anterograde as well as retrograde conduction [30].…”

Section: Optical Mapping Of the Human Avnmentioning

confidence: 99%

Optical Mapping of the Sinoatrial Node and Atrioventricular Node

2012

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Within the heart there burns a sort of vestal fire, so subtle that it escapes immediately through any incision made to reveal it. Hippocrates SummaryTechnological advances often precede scientific breakthroughs that have led to leaps in our understanding of human physiology. The advent of the electrical galvanometer was a landmark advancement that enabled careful study of the electrical activation of the heart. Similarly, optical imaging, or mapping, using fluorescent, voltage sensitive dyes has enabled the careful study of the sinoatrial (SA) and atrioventricular (AV) nodes, and improved our understanding of how anatomic structure is related to electrophysiological function. We review the major findings of optical mapping studies of the sinoatrial node (SAN) and atrioventricular node (AVN), with particular emphasis on clinically relevant physiology and pathophysiology. We pay particular attention to clinical implications of these seminal findings derived from animal models and from the optical mapping study of human hearts. The studies presented are intended to improve the reader's understanding of SAN and AVN physiology, as well as to offer insight into the advantages and limitations of optical mapping. Optical mapping methodologyThe sinoatrial node (SAN) and atrioventricular node (AVN) of large mammals such as canines and humans are complex, three-dimensional structures consisting of electrically specialized tissues that are largely insulated from the surrounding structures. The SAN and AVN are essentially encased in fibrofatty tissues, vasculature and connective tissue, and surrounded by atrial myocardium. This complex anatomy prevents surface electrodes from delineating activation within the SAN and AVN. Microelectrode recordings provide a reliable tool to visualize electrical responses of specialized cell types that are integral parts of these structures, but cannot reveal a broad pattern of activation due to the focal spatial nature of these recordings. Moreover, the depth of microelectrode impalement is difficult to verify, and cells located closer to the endocardial surface may be activated substantially later (SAN) or earlier (AVN) than those at depth. Optical mapping (OM) takes advantage of fluorescent, voltage sensitive dyes whose absorption and emission spectra change with changes in transmembrane voltage, to accurately image action potentials from a large area, in terms of anatomic surface and to a lesser extent, depth. Recorded optical action potentials (AP) are a composite of the APs from superficial and deeper anatomic structures, which can be deconstructed to reveal the electrical and functional properties of individual structures that make up the SAN and AVN. The ability to deconstruct these complex optical AP signals is critical to understanding the function of these complex structures. Optical mapping has enabled studies of the origin and propagation of electrical activity within and surrounding the SAN and AVN to improve our understanding of function during physiological and pathological sta...

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Anatomic Localization and Autonomic Modulation of Atrioventricular Junctional Rhythm in Failing Human Hearts

Cited by 47 publications

References 42 publications

Palette of fluorinated voltage-sensitive hemicyanine dyes

Palette of fluorinated voltage-sensitive hemicyanine dyes

Circulation: Heart Failure Editors' Picks

Optical Mapping of the Sinoatrial Node and Atrioventricular Node

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