title: Mechanism of interruption of atrial flutter by moricizine. Electrophysiological and multiplexing studies in the canine sterile pericarditis model of atrial flutter.
abstract: BACKGROUND
  Moricizine is said to have potent effects on cardiac conduction but little or no effect on cardiac refractoriness.
  
  
  RESULTS
  The effects of moricizine (2 mg/kg IV) on induced atrial flutter were studied 2 to 4 days after the creation of sterile pericarditis in 11 dogs. Ten episodes of stable atrial flutter before and after the administration of moricizine were studied in 9 dogs in the conscious, nonsedated state, and 7 episodes were studied in 6 dogs in the anesthetized, open chest state. In the conscious state, the effects of moricizine on atrial excitability, atrial effective refractory period, and intra-atrial conduction times were studied by recording during overdrive pacing of sinus rhythm from epicardial electrodes placed at selected atrial sites. Moricizine prolonged the atrial flutter cycle length in all the episodes, from a mean of 133 +/- 9 to 172 +/- 27 milliseconds (P < .001), and then terminated 7 of the 10 episodes. Moricizine increased the 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 from the sulcus terminalis to the posteroinferior left atrium) from a mean of 58 +/- 6 to 64 +/- 5 milliseconds (P < .005). Prolongation of the atrial effective refractory period from 166 +/- 20 to 174 +/- 24 milliseconds (P < .05) was observed only at the sulcus terminalis site. In the open chest studies, administration of moricizine prolonged the atrial flutter cycle length from a mean of 150 +/- 15 to 216 +/- 30 milliseconds (P < .001) and then terminated the atrial flutter in all 7 episodes. As demonstrated by simultaneous multisite mapping from 95 bipolar sites on the right atrial free wall, the atrial flutter cycle length prolongation was either due to further slowing of conduction in an area of slow conduction in the reentrant circuit of the atrial flutter (5 episodes) or further slowing of conduction in an area of slow conduction plus the development of a second area of slow conduction (2 episodes). The change in conduction times in the rest of the reentrant circuit was negligible (10.9 +/- 8.7% of the total change). In all 7 episodes, the last circulating reentrant wave front blocked in an area of slow conduction.
  
  
  CONCLUSIONS
  Moricizine (1) prolongs the atrial flutter cycle length, primarily by slowing conduction in an area of slow conduction in the reentrant 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 atrial flutter in this canine model. The reason for these effects of moricizine are not readily explained by its effects on global atrial conduction times and refractoriness studied during sinus rhythm. Local changes 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.
authors.affiliation: Department of Medicine, Case Western Reserve University, University Hospitals of Cleveland, Ohio 44106.
authors.forename: J
authors.initials: J
authors.lastname: Ortiz
authors.forename: A
authors.initials: A
authors.lastname: Nozaki
authors.forename: A
authors.initials: A
authors.lastname: Shimizu
authors.forename: C
authors.initials: C
authors.lastname: Khrestian
authors.forename: Y
authors.initials: Y
authors.lastname: Rudy
authors.forename: A L
authors.initials: AL
authors.lastname: Waldo
mesh_terms: D000818:Animals; D001282:Atrial Flutter / Q000188:drug therapy* / Q000503:physiopathology; D004285:Dogs; D006329:Heart Conduction System / Q000187:drug effects* / Q000503:physiopathology; D016293:Moricizine / Q000494:pharmacology / Q000627:therapeutic use*; D010493:Pericarditis / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D016293:Moricizine