EFFECTS OF AZIMILIDE DIHYDROCHLORIDE ON CIRCUS MOVEMENT ATRIAL-FLUTTER IN THE CANINE STERILE PERICARDITIS MODEL

Introduction: The effects of a Class III agent, azimilide dihydrochlor ide, on atrial flutter circuits were studied in a functional model of single loop reentrant atrial flutter using dogs, 3 to 5 days after pro duction of sterile pericarditis. Methods and Results: A computerized m apping system was used to construct activation maps from 138 to 222 ep icardial sites in the right atrium. Doses of 3, 10, and 30 mg/kg IV az imilide dihydrochloride were analyzed in 8 dogs in which sustained atr ial flutter lasting more than 30 minutes was induced by burst pacing, Atrial flutter was always due to a single loop circus movement reentry in the lower right atrium, At 3 mg/kg, azimilide dihydrochloride term inated atrial flutter in 2 dogs; however, atrial flutter was reinduced . At 10 mg/kg, atrial flutter was terminated in all 8 dogs but was rei nduced in 4 dogs with slower rate. At 30 mg/kg, atrial hotter was term inated in the remaining 4 dogs and could not be reinduced. Atrial flut ter cycle length always increased prior to termination. Isochronal act ivation maps showed that the increase in cycle length was due to addit ional conduction delays in the slow zone of the reentrant circuit. The site of termination was always located within the slow conduction zon e situated in the lower right atrium between the line of functional co nduction block and the AV ring, Effective refractory periods (ERPs) we re measured at selected sites in the slow zone and normal zone at twic e diastolic threshold for the 10 mg/kg dose, Azimilide preferentially prolonged ERP in the slow zone (42.4 +/- 20.1 msec, mean +/- SD) compa red with the normal zone (23.3 +/- 15.4 msec, P < 0.0001). The increas e in cycle length corresponded with the increase in ERP in the slow zo ne. Conclusions: In a functional model of circus movement atrial flutt er, azimilide dihydrochloride terminates and prevents reinduction of a trial flutter by a preferential increase in refractoriness leading to further conduction delay and conduction block in the slow zone of the functional reentrant circuit.