PMID- 19303369
OWN - NLM
STAT- MEDLINE
DCOM- 20090825
LR  - 20161222
IS  - 1556-3871 (Electronic)
IS  - 1547-5271 (Linking)
VI  - 6
IP  - 5
DP  - 2009 May
TI  - Early termination of spiral wave reentry by combined blockade of Na+ and L-type 
      Ca2+ currents in a perfused two-dimensional epicardial layer of rabbit 
      ventricular myocardium.
PG  - 684-92
LID - 10.1016/j.hrthm.2009.01.022 [doi]
AB  - BACKGROUND: Modification of spiral wave (SW) reentry by antiarrhythmic drugs is a 
      central issue to be challenged for better understanding of their benefits and 
      risks. OBJECTIVE: We investigated the effects of pilsicainide and/or verapamil, 
      which block sodium and L-type calcium currents (I(Na) and I(Ca,L)), respectively, 
      on SW reentry. METHODS: A two-dimensional epicardial ventricular muscle layer was 
      created in rabbit hearts by cryoablation (n = 32), and action potential signals 
      were analyzed by high-resolution optical mapping. RESULTS: During constant 
      stimulation, pilsicainide (3-5 microM) caused a frequency-dependent decrease of 
      conduction velocity (CV; by 20%-54% at 5 Hz) without affecting action potential 
      duration (APD). Verapamil (3 microM) caused APD shortening (by 16% at 5 Hz) 
      without affecting CV. Ventricular tachycardias (VTs) that were induced were more 
      sustained in the presence of either pilsicainide or verapamil. The incidence of 
      sustained VTs (>30 s)/all VTs per heart was 58% +/- 9% for 5 microM pilsicainide 
      vs. 22% +/- 9% for controls and 62% +/- 10% for 3 microM verapamil vs. 22% +/- 8% 
      for controls. The SWs with pilsicainide were characterized by slower rotation 
      around longer functional block lines (FBLs), whereas those with verapamil were 
      characterized by faster rotation around shorter FBLs. Combined application of 3 
      microM pilsicainide and 3 microM verapamil resulted in early termination of VTs 
      (sustained VTs/all VTs per heart: 2% +/- 2% vs. 29% +/- 9% for controls); SWs 
      showed extensive drift and decremental conduction, leading to their spontaneous 
      annihilation. CONCLUSION: Blockade of either I(Na) or I(Ca,L) stabilizes SWs in a 
      two-dimensional epicardial layer of rabbit ventricular myocardium to help their 
      persistence, whereas blockade of both currents destabilizes SWs to facilitate 
      their termination.
FAU - Ishiguro, Yuko S
AU  - Ishiguro YS
AD  - Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan.
FAU - Honjo, Haruo
AU  - Honjo H
FAU - Opthof, Tobias
AU  - Opthof T
FAU - Okuno, Yusuke
AU  - Okuno Y
FAU - Nakagawa, Harumichi
AU  - Nakagawa H
FAU - Yamazaki, Masatoshi
AU  - Yamazaki M
FAU - Harada, Masahide
AU  - Harada M
FAU - Takanari, Hiroki
AU  - Takanari H
FAU - Suzuki, Tomoyuki
AU  - Suzuki T
FAU - Morishima, Mikio
AU  - Morishima M
FAU - Sakuma, Ichiro
AU  - Sakuma I
FAU - Kamiya, Kaichiro
AU  - Kamiya K
FAU - Kodama, Itsuo
AU  - Kodama I
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090121
PL  - United States
TA  - Heart Rhythm
JT  - Heart rhythm
JID - 101200317
RN  - 0 (Calcium Channel Blockers)
RN  - 0 (Calcium Channels, L-Type)
RN  - 0 (Sodium Channel Blockers)
RN  - 0 (Sodium Channels)
RN  - 98PI200987 (Lidocaine)
RN  - AV0X7V6CSE (pilsicainide)
RN  - CJ0O37KU29 (Verapamil)
SB  - IM
CIN - Heart Rhythm. 2009 May;6(5):693-5. PMID: 19332392
MH  - Animals
MH  - Calcium Channel Blockers/*therapeutic use
MH  - Calcium Channels, L-Type/*drug effects
MH  - Disease Models, Animal
MH  - Electrophysiologic Techniques, Cardiac
MH  - Heart Rate/drug effects
MH  - Heart Ventricles/drug effects/*pathology/physiopathology
MH  - Lidocaine/*analogs & derivatives/therapeutic use
MH  - Pericardium/pathology
MH  - Rabbits
MH  - Sodium Channel Blockers/*therapeutic use
MH  - Sodium Channels/drug effects/metabolism
MH  - Tachycardia, Sinoatrial Nodal Reentry/*drug therapy/metabolism/pathology
MH  - Treatment Outcome
MH  - Verapamil/*therapeutic use
EDAT- 2009/03/24 09:00
MHDA- 2009/08/26 09:00
CRDT- 2009/03/24 09:00
PHST- 2008/10/11 00:00 [received]
PHST- 2009/01/17 00:00 [accepted]
PHST- 2009/03/24 09:00 [entrez]
PHST- 2009/03/24 09:00 [pubmed]
PHST- 2009/08/26 09:00 [medline]
AID - S1547-5271(09)00080-0 [pii]
AID - 10.1016/j.hrthm.2009.01.022 [doi]
PST - ppublish
SO  - Heart Rhythm. 2009 May;6(5):684-92. doi: 10.1016/j.hrthm.2009.01.022. Epub 2009 
      Jan 21.