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Optical mapping of the isolated coronary-perfused human sinus node.

ABSTRACT: We sought to confirm our hypothesis that the human sinoatrial node (SAN) is functionally insulated from the surrounding atrial myocardium except for several exit pathways that electrically bridge the nodal tissue and atrial myocardium.The site of origin and pattern of excitation within the human SAN has not been directly mapped.The SAN was optically mapped in coronary-perfused preparations from nonfailing human hearts (n = 4, age 54 ± 15 years) using the dye Di-4-ANBDQBS and blebbistatin. The SAN 3-dimensional structure was reconstructed using histology.Optical recordings from the SAN had diastolic depolarization and multiple upstroke components, which corresponded to the separate excitations of the SAN and atrial layers. Excitation originated in the middle of the SAN (66 ± 17 beats/min), and then spread slowly (1 to 18 cm/s) and anisotropically. After a 82 ± 17 ms conduction delay within the SAN, the atrial myocardium was excited via superior, middle, and/or inferior sinoatrial conduction pathways. Atrial excitation was initiated 9.4 ± 4.2 mm from the leading pacemaker site. The oval 14.3 ± 1.5 mm × 6.7 ± 1.6 mm × 1.0 ± 0.2 mm SAN structure was functionally insulated from the atrium by connective tissue, fat, and coronary arteries, except for these pathways.These data demonstrated for the first time, to our knowledge, the location of the leading SAN pacemaker site, the pattern of excitation within the human SAN, and the conduction pathways into the right atrium. The existence of these pathways explains why, even during normal sinus rhythm, atrial breakthroughs could arise from a region parallel to the crista terminalis that is significantly larger (26.1 ± 7.9 mm) than the area of the anatomically defined SAN.

SUBMITTER: Fedorov VV

PROVIDER: S-EPMC3008584 | biostudies-other | 2010 Oct

REPOSITORIES: biostudies-other

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Optical mapping of the isolated coronary-perfused human sinus node.

Fedorov Vadim V VV Glukhov Alexey V AV Chang Roger R Kostecki Geran G Aferol Hyuliya H Hucker William J WJ Wuskell Joseph P JP Loew Leslie M LM Schuessler Richard B RB Moazami Nader N Efimov Igor R IR

Journal of the American College of Cardiology 20101001 17

<h4>Objectives</h4>We sought to confirm our hypothesis that the human sinoatrial node (SAN) is functionally insulated from the surrounding atrial myocardium except for several exit pathways that electrically bridge the nodal tissue and atrial myocardium.<h4>Background</h4>The site of origin and pattern of excitation within the human SAN has not been directly mapped.<h4>Methods</h4>The SAN was optically mapped in coronary-perfused preparations from nonfailing human hearts (n = 4, age 54 ± 15 year ...[more]

PMID: 20946995

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Project description:Purpose: Sentinel lymph node biopsy (SLNB) has emerged as the preferred standard procedure in patients with breast cancer, melanoma and other types of cancer. Herein, we developed a method to intra-operatively map SLNs and differentiate tumor metastases within SLNs at the same time, with the aim to provide more accurate and real-time intraoperative guidance. Experimental Design: Hyaluronic acid (HA), a ligand of lymphatic vessel endothelial hyaluronan receptor (LYVE)-1, is employed as a SLN mapping agent after being conjugated with a near-infrared fluorophore (Cy5.5). Different sized HAs (5, 10 and 20K) were tested in normal mice and mice with localized inflammation to optimize LN retention time and signal to background ratio. Cetuximab, an antibody against epidermal growth factor receptor (EGFR), and trastuzumab, an antibody against human epidermal growth factor receptor 2 (HER2), were labeled with near-infrared fluorophore (IRDye800) for detecting metastatic tumors. LN metastasis model was developed by hock injection of firefly luciferase engineered human head neck squamous carcinoma cancer UM-SCC-22B cells or human ovarian cancer SKOV-3 cells. The metastases within LNs were confirmed by bioluminescence imaging (BLI). IRDye800-Antibodies were intravenously administered 24 h before local administration of Cy5.5-HA. Optical imaging was then performed to identify nodal metastases. Results: Binding of HA with LYVE-1 was confirmed by ELISA and fluorescence staining. HA with a size of 10K was chosen based on the favorable migration and retention profile. After sequential administration of IRDye800-antibodies intravenously and Cy5.5-HA locally to a mouse model with LN metastases and fluorescence optical imaging, partially metastasized LNs were successfully distinguished from un-metastasized LNs and fully tumor occupied LNs, based on the different signal patterns. Conclusions: Fluorophore conjugated HA is a potential lymphatic mapping agent for SLNB. Dual-tracer imaging with the combination of lymphatic mapping agents and tumor targeting agents can identify tumor metastases within SLNs, thus may provide accurate and real-time intra-operative guidance to spare the time spent waiting for a biopsy result.

Dataset Information

Optical mapping of the isolated coronary-perfused human sinus node.

Publications

Optical mapping of the isolated coronary-perfused human sinus node.

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