ARDC Research Link Australia

ORCID Profile
Orcid icon. 0000-0001-5832-4786

Current Organisations
Addenbrooke's Hospital , Royal Brompton Hospital , London School of Hygiene and Tropical Medicine , Imperial College London , University of Cambridge , University of London , Guy's Hospital , General Hospital Birmingham , Royal College of Physicians , Pamela Youde Nethersole Eastern Hospital

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Publications

Publication

Prevalence and Outcomes of Infection Among Patients in Intensive Care Units in 2017

Publisher: American Medical Association (AMA)

Date: 21-04-2020

DOI: 10.1001/JAMA.2020.2717

Publication

Electrogram prolongation and nifedipine-suppressible ventricular arrhythmias in mice following targeted disruption of KCNE1

Publisher: Wiley

Date: 15-10-2003

DOI: 10.1113/JPHYSIOL.2003.048249

Publication

Slowed conduction and ventricular tachycardia after targeted disruption of the cardiac sodium channel gene Scn5a

Publisher: Proceedings of the National Academy of Sciences

Date: 23-04-2002

DOI: 10.1073/PNAS.082121299

Abstract: Voltage-gated sodium channels drive the initial depolarization phase of the cardiac action potential and therefore critically determine conduction of excitation through the heart. In patients, deletions or loss-of-function mutations of the cardiac sodium channel gene, SCN5A , have been associated with a wide range of arrhythmias including bradycardia (heart rate slowing), atrioventricular conduction delay, and ventricular fibrillation. The pathophysiological basis of these clinical conditions is unresolved. Here we show that disruption of the mouse cardiac sodium channel gene, Scn5a , causes intrauterine lethality in homozygotes with severe defects in ventricular morphogenesis whereas heterozygotes show normal survival. Whole-cell patch cl analyses of isolated ventricular myocytes from adult Scn5a +/− mice demonstrate a ≈50% reduction in sodium conductance. Scn5a +/− hearts have several defects including impaired atrioventricular conduction, delayed intramyocardial conduction, increased ventricular refractoriness, and ventricular tachycardia with characteristics of reentrant excitation. These findings reconcile reduced activity of the cardiac sodium channel leading to slowed conduction with several apparently erse clinical phenotypes, providing a model for the detailed analysis of the pathophysiology of arrhythmias.