University of Surrey

Test tubes in the lab Research in the ATI Dance Research

Altered re-excitation thresholds and conduction of extrasystolic action potentials contribute to arrhythmogenicity in murine models of long QT syndrome.

Duehmke, RM, Pearcey, S, Stefaniak, JD, Guzadhur, L, Jeevaratnam, K, Costopoulos, C, Pedersen, TH, Grace, AA and Huang, CL (2012) Altered re-excitation thresholds and conduction of extrasystolic action potentials contribute to arrhythmogenicity in murine models of long QT syndrome. Acta Physiol (Oxf), 206 (3). pp. 164-177.

Full text not available from this repository.


AIM: QT interval prolongation reflecting delayed action potential (AP) repolarization is associated with polymorphic ventricular tachycardia and early after depolarizations potentially initiating extrasystolic APs if of sufficient amplitude. The current experiments explored contributions of altered re-excitation thresholds for, and conduction of, such extrasystolic APs to arrhythmogenesis in Langendorff-perfused, normokalaemic, control wild-type hearts and two experimental groups modelling long QT (LQT). The two LQT groups consisted of genetically modified, Scn5a(+/ΔKPQ) and hypokalaemic wild-type murine hearts. METHODS: Hearts were paced from their right ventricles and monophasic AP electrode recordings obtained from their left ventricular epicardia, with recording and pacing electrodes separated by 1 cm. An adaptive programmed electrical stimulation protocol applied pacing (S1) stimulus trains followed by premature (S2) extrastimuli whose amplitudes were progressively increased with progressive decrements in S1S2 interval to maintain stimulus capture. Such protocols culminated in either arrhythmic or refractory endpoints. RESULTS: Arrhythmic outcomes were associated with (1) lower conduction velocities in their initiating extrasystolic APs than refractory outcomes and (2) higher conduction velocities in the LQT groups than in controls. Furthermore, (3) the endpoints were reached at longer S1S2 coupling intervals and with smaller stimulus amplitudes in the LQT groups compared with controls. This was despite (4) similar relationships between conduction velocity and S1S2 coupling interval and between re-excitation thresholds and S1S2 coupling interval in all three experimental groups. CONCLUSIONS: Arrhythmias induced by extrasystolic APs in the LQT groups thus occur under conditions of higher conduction velocity and greater sensitivity to extrastimuli than in controls.

Item Type: Article
Divisions : Surrey research (other units)
Authors :
Duehmke, RM
Pearcey, S
Stefaniak, JD
Guzadhur, L
Costopoulos, C
Pedersen, TH
Grace, AA
Huang, CL
Date : November 2012
DOI : 10.1111/j.1748-1716.2012.02443.x
Uncontrolled Keywords : Action Potentials, Animals, Arrhythmias, Cardiac, Electric Stimulation, Endpoint Determination, Female, Heart Conduction System, Hypokalemia, Long QT Syndrome, Male, Mice, Mice, Inbred Strains, Mice, Mutant Strains, Models, Animal, NAV1.5 Voltage-Gated Sodium Channel, Neural Conduction, Time Factors, Ventricular Premature Complexes
Related URLs :
Depositing User : Symplectic Elements
Date Deposited : 17 May 2017 10:27
Last Modified : 24 Jan 2020 19:20

Actions (login required)

View Item View Item


Downloads per month over past year

Information about this web site

© The University of Surrey, Guildford, Surrey, GU2 7XH, United Kingdom.
+44 (0)1483 300800