Effects of antiarrhythmic drugs on canine atrial flutter due to reentry: role of prolongation of refractory period and depression of conduction to excitable gap

Second Department of Internal Medicine, Tokyo University Hospital, Japan.

Antiarrhythmic drugs prolong the effective refractory period and depress conduction. To determine the exact role played by these two electrophysiologic effects in the termination of reentry, the effects of disopyramide, flecainide, propafenone and E-4031, a new class III drug, were examined in a canine model of atrial flutter (cycle length 120 +/- 4 to 131 +/- 3 ms) caused by reentry. Atrial flutter was induced in 32 anesthetized open chest dogs after placement of an intercaval crush. The excitable gap ranged from 9 +/- 2% to 11 +/- 4% of the basic flutter cycle length. The effective refractory period in the reentrant circuit during atrial flutter was estimated by subtracting the excitable gap from the basic flutter cycle length. Prolongation of flutter cycle length by the test drugs was proportional to the interatrial conduction time (r = 0.87, p less than 0.001). Atrial flutter was terminated by each test drug in all dogs except for flecainide and propafenone in one dog each. E-4031 prolonged the refractory period during atrial flutter to 129 +/- 6 ms, which did not differ significantly from the flutter cycle length immediately before termination (134 +/- 4 ms). The refractory period during atrial flutter after injection of the other drugs was shorter than the flutter cycle length before termination of atrial flutter (for example, flecainide 126 +/- 5 vs. 179 +/- 11 ms, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

This article has been cited by other articles:

				A. Mazza, M. S. Fera, I. Bisceglia, F. Bettiol, G. Pulignano, P. Tanzi, C. Gaudio, and E. Giovannini Efficacy and safety of ibutilide vs. transoesophageal atrial pacing for the termination of type I atrial flutter Europace, January 1, 2004; 6(4): 301 - 306. [Abstract] [Full Text] [PDF]

				M. M. Rahme, G. Ungab, M. Wadhwa, F. Al-Kandari, B. Yao, A. Gupta, K. Lee, H.-Y. Kim, and G. K. Feld Electrophysiologic and Antiarrhythmic Effects of the New Class III Antiarrhythmic Drug KCB-328 in Experimental Canine Atrial Flutter Journal of Cardiovascular Pharmacology and Therapeutics, September 1, 2001; 6(3): 297 - 306. [Abstract] [PDF]

				M. Valderrabano and B. N. Singh Review : Electrophysiologic and Antiarrhythmic Effects of Propafenone: Focus on Atrial Fibrillation Journal of Cardiovascular Pharmacology and Therapeutics, January 1, 1999; 4(3): 183 - 198. [PDF]

				C.-T. Tai, S.-A. Chen, A.-N. Feng, W.-C. Yu, Y.-J. Chen, and M.-S. Chang Electropharmacologic Effects of Class I and Class III Antiarrhythmia Drugs on Typical Atrial Flutter : Insights Into the Mechanism of Termination Circulation, May 19, 1998; 97(19): 1935 - 1945. [Abstract] [Full Text] [PDF]

				K. T. Murray Ibutilide Circulation, February 10, 1998; 97(5): 493 - 497. [Full Text] [PDF]

				B. S. Stambler, M. A. Wood, and K. A. Ellenbogen Antiarrhythmic Actions of Intravenous Ibutilide Compared With Procainamide During Human Atrial Flutter and Fibrillation : Electrophysiological Determinants of Enhanced Conversion Efficacy Circulation, December 16, 1997; 96(12): 4298 - 4306. [Abstract] [Full Text]

				J. Toyama, K. Kamiya, J. Cheng, J.-K. Lee, R. Suzuki, and I. Kodama Vesnarinone Prolongs Action Potential Duration Without Reverse Frequency Dependence in Rabbit Ventricular Muscle by Blocking the Delayed Rectifier K+ Current Circulation, November 18, 1997; 96(10): 3696 - 3703. [Abstract] [Full Text]

				C.-T. Tai, S.-A. Chen, C.-E. Chiang, S.-H. Lee, K.-C. Ueng, Z.-C. Wen, J.-L. Huang, Y.-J. Chen, W.-C. Yu, A.-N. Feng, et al. Characterization of Low Right Atrial Isthmus as the Slow Conduction Zone and Pharmacological Target in Typical Atrial Flutter Circulation, October 21, 1997; 96(8): 2601 - 2611. [Abstract] [Full Text]

				K. Mori, Y. Hara, T. Saito, Y. Masuda, and H. Nakaya Anticholinergic Effects of Class III Antiarrhythmic Drugs in Guinea Pig Atrial Cells : Different Molecular Mechanisms Circulation, June 1, 1995; 91(11): 2834 - 2843. [Abstract] [Full Text]