TY - JOUR
T1 - Ventricular arrhythmogenesis following slowed conduction in heptanol-treated, Langendorff-perfused mouse hearts
AU - Tse, Gary
AU - Hothi, Sandeep S.
AU - Grace, Andrew A.
AU - Huang, Christopher L.H.
N1 - Funding Information:
Acknowledgments This work was supported by the Wellcome Trust, the Medical Research Council, the British Heart Foundation, the Helen Kirkland Trust, Papworth Hospital, UK, and Xention Discovery. GT was supported by a Wellcome Trust Vacation Scholarship, Trinity Hall, Cambridge, a Biotechnology and Biological Sciences Research Council CASE Studentship, and Xention Discovery. SSH was supported by a Medical Research Council Capacity Building Studentship.
PY - 2012/3
Y1 - 2012/3
N2 - Arrhythmogenic effects of slowed action potential conduction produced by the gap junction and sodium-channel inhibitor heptanol (0.1-2 mM) were explored in Langendorff-perfused mouse hearts. Monophasic action potential recordings showed that 2 mM heptanol induced ventricular tachycardia in the absence of triggered activity arising from early or after-depolarizations during regular 8 Hz pacing and programmed electrical stimulation (PES). It also increased activation latencies and ventricular effective refractory periods (VERPs), but did not alter action potential duration (APD), thereby reducing local critical intervals for re-excitation given by APD 90- VERP. Bipolar electrogram recordings showed that 2 mMheptanol increased electrogram duration (EGD) and ratios of EGDs obtained at the longest to those obtained at the shortest S1S2 intervals studied during PES, suggesting increased dispersion of conduction velocities. These findings show, for the first time in the mouse heart, that slowed conduction induces reversible arrhythmogenic effects despite repolarization abnormalities expected to reduce arrhythmogenicity.
AB - Arrhythmogenic effects of slowed action potential conduction produced by the gap junction and sodium-channel inhibitor heptanol (0.1-2 mM) were explored in Langendorff-perfused mouse hearts. Monophasic action potential recordings showed that 2 mM heptanol induced ventricular tachycardia in the absence of triggered activity arising from early or after-depolarizations during regular 8 Hz pacing and programmed electrical stimulation (PES). It also increased activation latencies and ventricular effective refractory periods (VERPs), but did not alter action potential duration (APD), thereby reducing local critical intervals for re-excitation given by APD 90- VERP. Bipolar electrogram recordings showed that 2 mMheptanol increased electrogram duration (EGD) and ratios of EGDs obtained at the longest to those obtained at the shortest S1S2 intervals studied during PES, suggesting increased dispersion of conduction velocities. These findings show, for the first time in the mouse heart, that slowed conduction induces reversible arrhythmogenic effects despite repolarization abnormalities expected to reduce arrhythmogenicity.
KW - Heptanol
KW - Mice
KW - Slowed conduction
KW - Ventricular arrhythmia
UR - https://www.scopus.com/pages/publications/84860727948
U2 - 10.1007/s12576-011-0187-2
DO - 10.1007/s12576-011-0187-2
M3 - Article
C2 - 22219003
AN - SCOPUS:84860727948
SN - 1880-6546
VL - 62
SP - 79
EP - 92
JO - Journal of Physiological Sciences
JF - Journal of Physiological Sciences
IS - 2
ER -