Daily oral verapamil before but not after rapid atrial excitation prevents electrical remodeling.
BACKGROUND
Intravenous verapamil has been reported to prevent electrical remodeling induced by rapid atrial excitation of several minutes to several hours. However, the clinical efficacy of verapamil when taken orally and daily remains controversial.


OBJECTIVE
We attempted to demonstrate our hypothesis that if verapamil prevents calcium (Ca) overload, its efficacy would be greater when taken before, rather than after, the onset of rapid atrial excitation.


METHODS
In 24 dogs, pacing and recording electrodes were sutured onto the right atrium. After a 5-day recovery period, rapid atrial pacing at 400 ppm was started, followed 2 days later by oral verapamil (8 mg/kg per day) in eight dogs (After group; A). In another eight dogs, oral verapamil administration was begun 1 week before the initiation of rapid pacing (Before group; B). In the remaining eight dogs, only rapid atrial pacing was started, without oral verapamil (Control group; C). We measured the effective refractory period (ERP) and conduction velocity (CV), and calculated wavelength (WL) at cycle lengths 200 and 300 ms on the day before (P0), and after 2 (P2), 7 (P7), 14(P14) days of rapid pacing.


RESULTS
In response to rapid atrial pacing, ERP, CV, WL decreased and progressively and comparably in A and C (P<0.05 vs. P0). In contrast, in B, these parameters did not change significantly and remained greater than those in A and C (P<0.05). Moreover, the adaptation of ERP to rate was preserved only in B. The duration of atrial fibrillation (AF) was shorter in B than in A and C (P<0.05). The inducibility of AF tended to be lower, and the fibrillation cycle length was longer in B than in A and C.


CONCLUSIONS
Oral verapamil started before but not after rapid atrial excitation prevents electrical remodeling. Verapamil may exert beneficial effects when it is taken during sinus rhythm, but not after more than 2 days of atrial tachyarrhythmia.
Kurita
Yasuo
Y
Cardiology Division, Department of Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, 160-8582 Tokyo, Japan.
Mitamura
Hideo
H
Shiroshita-Takeshita
Akiko
A
Yamane
Akiko
A
Ieda
Masaki
M
Kinebuchi
Osamu
O
Sato
Toshiaki
T
Miyoshi
Shunichiro
S
Hara
Motoki
M
Takatsuki
Seiji
S
Ogawa
Satoshi
S
D000200:Action Potentials / Q000187:drug effects*; D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D001281:Atrial Fibrillation / Q000378:metabolism / Q000517:prevention & control*; D002121:Calcium Channel Blockers / Q000008:administration & dosage*; D002304:Cardiac Pacing, Artificial; D004285:Dogs; D004562:Electrocardiography; D023421:Models, Animal; D013997:Time Factors; D014700:Verapamil / Q000008:administration & dosage*
D002121:Calcium Channel Blockers; D014700:Verapamil