Effects of azimilide dihydrochloride on circus movement atrial flutter in the canine sterile pericarditis model

The effects of a Class III agent, azimilide dihydrochloride, on atrial flutter circuits were studies in a functional model of single loop reentrant atrial flutter using dogs, 3 to 5 days after production of sterile pericarditis.

A computerized mapping system was used to construct activation maps from 138 to 222 epicardial sites in the right atrium. Doses of 3, 10, and 30 mg/kg i.v. azimilide dihydrochloride were analyzed in 8 dogs in which sustained atrial flutter lasting more than 30 minutes was induced by burst pacing. Atrial flutter was always due to single loop circus movement reentry in the lower right atrium. At 3 mg/kg, azimilide dihydrochloride terminated atrial flutter in 2 dogs; however, atrial flutter was reinduced. At 10 mg/kg, atrial flutter was terminated in all 8 dogs but was reinduced in 4 dogs with slower rate. At 30 mg/kg, atrial flutter was terminated in the remaining 4 dogs and could not be reinduced. Atrial flutter cycle length always increased prior to termination. Isochronal activation maps showed that the increase in cycle length was due to additional conduction delays in the slow zone of the reentrant circuit. The site of termination was always located within the slow conduction zone situated in the lower right atrium between the line of functional conduction block and the AV ring. Effective refractory periods (ERPs) were measured at selected sites in the slow zone and normal zone at twice diastolic threshold for the 10 mg/kg dose. Azimilide preferentially prolonged ERP in the slow zone (42.4 +/- 20.1 msec, mean +/- SD) compared with the normal zone (23.3 +/- 15.4 msec, P < 0.0001). The increase in cycle length corresponded with the increase in ERP in the slow zone.

In a functional model of circus movement atrial flutter, azimilide dihydrochloride terminates and prevents reinduction of atrial flutter by a preferential increase in refractoriness leading to further conduction delay and conduction block in the slow zone of the functional reentrant circuit.