Imperial College London

Dr Fu Siong Ng

Faculty of MedicineNational Heart & Lung Institute

Clinical Senior Lecturer in Cardiac Electrophysiology
 
 
 
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Contact

 

+44 (0)20 7594 3614f.ng Website

 
 
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Location

 

ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@inproceedings{Ng:2010,
author = {Ng, FS and Lyon, AR and Shadi, IT and Chang, ETY and Chowdhury, RA and Dupont, E and Peters, NS and Ng, FS and Lyon, AR and Shadi, IT and Chang, ETY and Chowdhury, RA and Dupont, E and Peters, NS},
pages = {234--234},
title = {Moderate gap junctional uncoupling with carbenoxolone slows conduction and increases vulnerability to ventricular arrhythmias—an optical mapping study},
url = {https://docs.google.com/viewer?a=v&pid=gmail&attid=0.1&thid=12806984329ab11b&mt=application%2Fpdf&url=https%3A%2F%2Fmail.google.com%2Fmail%2F%3Fui%3D2%26ik%3D9dc80d9ba8%26view%3Datt%26th%3D12806984329ab11b%26attid%3D0.1%26disp%3Dattd%26zw&sig=AHIEtbRlSQf2UQ1jSGKKk3JXrgJE6pIjUA&pli=1},
year = {2010}
}

RIS format (EndNote, RefMan)

TY  - CPAPER
AB - It is uncertain whether moderate conductionslowing through gap junctional uncoupling on its own, inthe absence of action potential or structural changes, issufficient to be pro-arrhythmic. We used optical mapping:(1) to study the effects of carbenoxolone (CBX), a gapjunction uncoupler, on conduction velocity and actionpotential duration and (2) to assess the effects of moderateconduction slowing and gap junctional uncoupling onarrhythmia vulnerability in structurally normal hearts.Methods: Rat hearts (n = 12) were perfused on aLangendorff apparatus, loaded with a voltage-sensitivedye (RH237) and perfused with an excitation–contractionuncoupler (10 μM blebbistatin). Transmembrane voltagetransients were recorded using a 256-photodiode array.Hearts were then perfused with 30 μM CBX (n=6) orcontrol (n=6) for 30 min and epicardial activation mappedevery 2 min during ventricular pacing. Subsequently, heartswere subjected to programmed ventricular stimulation andassigned an inducibility quotient depending on ease ofarrhythmia inducibility. Results: CBX slowed conductionvelocity (conduction velocity index: baseline 100%, CBX70±2%, P<0.01), with no change in control hearts after30 min (baseline 100%, controls 98±3%, P=NS). CBX didnot affect action potential duration (APD90: baseline 90±3 ms, CBX 94±5 ms, P=NS). Inducibility of ventriculararrhythmias was increased in CBX hearts compared withcontrol hearts (inducibility quotient: CBX 5.0±1.0, control2.5±1.0, P<0.05). Conclusions: Gap junctional uncouplingwith CBX produced a 30% reduction in conductionvelocity without changes in action potential duration andresulted in increased arrhythmia vulnerability. These results suggest that moderate conduction slowing produced by gap junctional uncoupling in isolation, i.e. in the absence of changes in action potential duration or structural abnormalities, is sufficient to increase susceptibility to ventricular arrhythmias.
AU - Ng,FS
AU - Lyon,AR
AU - Shadi,IT
AU - Chang,ETY
AU - Chowdhury,RA
AU - Dupont,E
AU - Peters,NS
AU - Ng,FS
AU - Lyon,AR
AU - Shadi,IT
AU - Chang,ETY
AU - Chowdhury,RA
AU - Dupont,E
AU - Peters,NS
EP - 234
PY - 2010///
SP - 234
TI - Moderate gap junctional uncoupling with carbenoxolone slows conduction and increases vulnerability to ventricular arrhythmias—an optical mapping study
ER -