OBJECTIVES: The purpose of this study was to determine the electrophysiologic effects of simvastatin in canine pulmonary vein (PV) sleeve preparations. BACKGROUND: Ectopic activity arising from the PV plays a prominent role in the development of atrial fibrillation. METHODS: Transmembrane action potentials were recorded from canine superfused left superior or inferior PV sleeves using standard microelectrode techniques. Acetylcholine (1 μM), isoproterenol (1 μM), high calcium ([Ca(2+)](o) = 5.4 mM), or a combination was used to induce early afterdepolarizations or delayed afterdepolarizations and triggered activity. Voltage clamp experiments were performed in the left atrium measuring fast and late sodium currents. RESULTS: Under steady-state conditions, simvastatin (10 nM, n = 9) induced a small increase in action potential duration measured at 85% repolarization and a significant decrease in action potential amplitude, take-off potential, and maximum rate of rise of action potential upstroke at the fastest rates. The V(max) decreased from 175.1 ± 34 V/s to 151.7 ± 28 V/s and from 142 ± 47 V/s to 97.4 ± 39 V/s at basic cycle lengths of 300 and 200 ms, respectively. Simvastatin (10 to 20 nM) eliminated delayed afterdepolarizations and delayed afterdepolarization-induced triggered activity in 7 of 7 PV sleeve preparations and eliminated or reduced late-phase 3 early afterdepolarizations in 6 of 6 PV sleeve preparations. Simvastatin (20 nM) did not affect late or fast sodium currents measured using voltage clamp techniques. CONCLUSIONS: Our data suggest that in addition to its upstream actions to reduce atrial structural remodeling, simvastatin exerts a direct antiarrhythmic effect by suppressing triggers responsible for the genesis of atrial fibrillation.
OBJECTIVES: The purpose of this study was to determine the electrophysiologic effects of simvastatin in canine pulmonary vein (PV) sleeve preparations. BACKGROUND: Ectopic activity arising from the PV plays a prominent role in the development of atrial fibrillation. METHODS: Transmembrane action potentials were recorded from canine superfused left superior or inferior PV sleeves using standard microelectrode techniques. Acetylcholine (1 μM), isoproterenol (1 μM), high calcium ([Ca(2+)](o) = 5.4 mM), or a combination was used to induce early afterdepolarizations or delayed afterdepolarizations and triggered activity. Voltage clamp experiments were performed in the left atrium measuring fast and late sodium currents. RESULTS: Under steady-state conditions, simvastatin (10 nM, n = 9) induced a small increase in action potential duration measured at 85% repolarization and a significant decrease in action potential amplitude, take-off potential, and maximum rate of rise of action potential upstroke at the fastest rates. The V(max) decreased from 175.1 ± 34 V/s to 151.7 ± 28 V/s and from 142 ± 47 V/s to 97.4 ± 39 V/s at basic cycle lengths of 300 and 200 ms, respectively. Simvastatin (10 to 20 nM) eliminated delayed afterdepolarizations and delayed afterdepolarization-induced triggered activity in 7 of 7 PV sleeve preparations and eliminated or reduced late-phase 3 early afterdepolarizations in 6 of 6 PV sleeve preparations. Simvastatin (20 nM) did not affect late or fast sodium currents measured using voltage clamp techniques. CONCLUSIONS: Our data suggest that in addition to its upstream actions to reduce atrial structural remodeling, simvastatin exerts a direct antiarrhythmic effect by suppressing triggers responsible for the genesis of atrial fibrillation.
Authors: M Haïssaguerre; P Jaïs; D C Shah; S Garrigue; A Takahashi; T Lavergne; M Hocini; J T Peng; R Roudaut; J Clémenty Journal: Circulation Date: 2000-03-28 Impact factor: 29.690
Authors: A C Zygmunt; G T Eddlestone; G P Thomas; V V Nesterenko; C Antzelevitch Journal: Am J Physiol Heart Circ Physiol Date: 2001-08 Impact factor: 4.733
Authors: Mélèze Hocini; Siew Y Ho; Tokuhiro Kawara; André C Linnenbank; Mark Potse; Dipen Shah; Pierre Jaïs; Michiel J Janse; Michel Haïssaguerre; Jacques M T De Bakker Journal: Circulation Date: 2002-05-21 Impact factor: 29.690
Authors: Prashant D Bhave; L Elizabeth Goldman; Eric Vittinghoff; Judith H Maselli; Andrew Auerbach Journal: Heart Rhythm Date: 2011-09-09 Impact factor: 6.343
Authors: Fernando O Campos; Anton J Prassl; Gunnar Seemann; Rodrigo Weber dos Santos; Gernot Plank; Ernst Hofer Journal: Med Biol Eng Comput Date: 2012-03-13 Impact factor: 2.602
Authors: John C Bonano; Ashley K Aratani; Tanmaya D Sambare; Stuart B Goodman; James I Huddleston; William J Maloney; David R Burk; Alistair J Aaronson; Andrea K Finlay; Derek F Amanatullah Journal: J Arthroplasty Date: 2021-05-25 Impact factor: 4.757
Authors: M Alings; M D Smit; M L Moes; H J G M Crijns; J G P Tijssen; J Brügemann; H L Hillege; D A Lane; G Y H Lip; J R L M Smeets; R G Tieleman; R Tukkie; F F Willems; R A Vermond; D J Van Veldhuisen; I C Van Gelder Journal: Neth Heart J Date: 2013-07 Impact factor: 2.380