Combined effects of nifekalant and lidocaine on the spiral-type re-entry in a perfused 2-dimensional layer of rabbit ventricular myocardium.
BACKGROUND
Spiral re-entry plays the principal role in the genesis of ventricular tachycardia and ventricular fibrillation (VT/VF). The specific I(Kr) blocker, nifekakant (NIF) has, often in combination with lidocaine (LID), recently been used in Japan to prevent recurrent VT/VF, but the combined effects of these drugs on spiral re-entry had never been investigated.


RESULTS
A ventricular epicardial sheet was obtained from 13 Langendorff-perfused rabbit hearts by means of a cryoprocedure, and epicardial excitations were analyzed with a high-resolution optical mapping system. Nifekakant (0.5 micromol/L) caused significant prolongation of action potential duration (APD) and LID (3 micromol/L) attenuated the APD prolongation without affecting the conduction velocity. VT were induced in 6 hearts by cross-field stimulation, and single- or double-loop spirals circulating around variable functional block lines were visualized during the VT. Nifekakant reduced VT cycle length and caused early termination in association with destabilization of the spiral dynamics (prolongation of functional block line, frequent local conduction block, and extensive meandering). These modifications of spiral-type re-entrant VT by NIF were prevented by addition of LID.


CONCLUSIONS
The effects of NIF on the spiral excitations are reversed by LID. This interaction should be taken into account when these drugs are used in combination to treat VT/VF.
Amino
Mari
M
Department of Cardiology, Tokai University School of Medicine, Shimokasuya, Isehara, Japan. mariam@is.icc.u-tokai.ac.jp
Yamazaki
Masatoshi
M
Nakagawa
Harumichi
H
Honjo
Haruo
H
Okuno
Yusuke
Y
Yoshioka
Koichiro
K
Tanabe
Teruhisa
T
Yasui
Kenji
K
Lee
Jong-Kook
JK
Horiba
Mitsuru
M
Kamiya
Kaichiro
K
Kodama
Itsuo
I
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D005260:Female; D006321:Heart / Q000000981:diagnostic imaging*; D006329:Heart Conduction System / Q000000981:diagnostic imaging* / Q000187:drug effects; D007090:Image Interpretation, Computer-Assisted / Q000295:instrumentation / Q000379:methods; D008012:Lidocaine / Q000494:pharmacology*; D008297:Male; D011744:Pyrimidinones / Q000494:pharmacology*; D011817:Rabbits; D011859:Radiography
D000889:Anti-Arrhythmia Agents; D011744:Pyrimidinones; C076259:nifekalant; D008012:Lidocaine