title: 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.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan.
authors.forename: Yuko S
authors.initials: YS
authors.lastname: Ishiguro
authors.forename: Haruo
authors.initials: H
authors.lastname: Honjo
authors.forename: Tobias
authors.initials: T
authors.lastname: Opthof
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Okuno
authors.forename: Harumichi
authors.initials: H
authors.lastname: Nakagawa
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Yamazaki
authors.forename: Masahide
authors.initials: M
authors.lastname: Harada
authors.forename: Hiroki
authors.initials: H
authors.lastname: Takanari
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Suzuki
authors.forename: Mikio
authors.initials: M
authors.lastname: Morishima
authors.forename: Ichiro
authors.initials: I
authors.lastname: Sakuma
authors.forename: Kaichiro
authors.initials: K
authors.lastname: Kamiya
authors.forename: Itsuo
authors.initials: I
authors.lastname: Kodama
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D020746:Calcium Channels, L-Type / Q000187:drug effects*; D004195:Disease Models, Animal; D022062:Electrophysiologic Techniques, Cardiac; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D008012:Lidocaine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010496:Pericardium / Q000473:pathology; D011817:Rabbits; D026941:Sodium Channel Blockers / Q000627:therapeutic use*; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism; D013615:Tachycardia, Sinoatrial Nodal Reentry / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016896:Treatment Outcome; D014700:Verapamil / Q000627:therapeutic use*
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D008012:Lidocaine; C042288:pilsicainide; D014700:Verapamil