MECHANISM OF INTERRUPTION OF ATRIAL-FLUTTER BY MORICIZINE - ELECTROPHYSIOLOGICAL AND MULTIPLEXING STUDIES IN THE CANINE STERILE PERICARDITIS MODEL OF ATRIAL-FLUTTER
J. Ortiz et al., MECHANISM OF INTERRUPTION OF ATRIAL-FLUTTER BY MORICIZINE - ELECTROPHYSIOLOGICAL AND MULTIPLEXING STUDIES IN THE CANINE STERILE PERICARDITIS MODEL OF ATRIAL-FLUTTER, Circulation, 89(6), 1994, pp. 2860-2869
Background Moricizine is said to have potent effects on cardiac conduc
tion but little or no effect on cardiac refractoriness. Methods and Re
sults The effects of moricizine (2mg/kgIV) on induced atrial flutter w
ere studied 2 to 4 days after the creation of sterile pericarditis in
11 dogs. Ten episodes of stable atrial flutter before and after the ad
ministration of moricizine were studied in 9 dogs in the conscious, no
nsedated state, and 7 episodes were studied in 6 dogs in the anestheti
zed, open chest state. In the conscious state, the effects of moricizi
ne on atrial excitability, atrial effective refractory period, and int
ra-atrial conduction times were studied by recording during overdrive
pacing of sinus rhythm from epicardial electrodes placed at selected a
trial sites. Moricizine prolonged the atrial flutter cycle length in a
ll the episodes, from a mean of 133+/-9 to 172+/-27 milliseconds (P<.0
01), and then terminated 7 of the 10 episodes. Moricizine increased th
e atrial threshold of excitability from a mean of 2.3+/-1.4 to 3.3+/-2
.2 mA (P<.01) and prolonged intra-atrial conduction times (measured fr
om the sulcus terminalis to the posteroinferior left atrium) from a me
an of 58+/-6 to 64+/-5 milliseconds (P<.005). Prolongation of the atri
al effective refractory period from 166+/-20 to 174+/-24 milliseconds
(P<.05) was observed only at the sulcus terminalis site. In the open c
hest studies, administration of moricizine prolonged the atrial flutte
r cycle length from a mean of 150+/-15 to 216+/-30 milliseconds (P<.00
1) and then terminated the atrial flutter in all 7 episodes. As demons
trated by simultaneous multisite mapping from 95 bipolar sites on the
right atrial free wall, the atrial flutter cycle length prolongation w
as either due to further slowing of conduction in an area of slow cond
uction in the reentrant circuit of the atrial flutter (5 episodes) or
further slowing of conduction in an area of slow conduction plus the d
evelopment of a second area of slow conduction (2 episodes). The chang
e in conduction times in the rest of the reentrant circuit was negligi
ble (10.9+/-8.7% of the total change). In all 7 episodes, the last cir
culating reentrant wave front blocked in an area of slow conduction. C
onclusions Moricizine (1) prolongs the atrial flutter cycle length, pr
imarily by slowing conduction in an area of slow conduction in the ree
ntrant circuit, (2) terminates atrial flutter by causing block of the
circulating reentrant wave front in an area of slow conduction of the
reentrant circuit, and (3) effectively interrupts otherwise stable atr
ial flutter in this canine model. The reason for these effects of mori
cizine are not readily explained by its effects on global atrial condu
ction times and refractoriness studied during sinus rhythm. Local chan
ges in conduction in an area(s) of slow conduction are responsible for
both cycle length prolongation and atrial flutter termination rather
than the traditional wavelength concept of head-tail interaction.