MECHANISM OF INTERRUPTION OF ATRIAL-FLUTTER BY MORICIZINE - ELECTROPHYSIOLOGICAL AND MULTIPLEXING STUDIES IN THE CANINE STERILE PERICARDITIS MODEL OF ATRIAL-FLUTTER

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.