title: Sustained atrial flutter around the tricuspid valve in pigs: differentiation of procainamide (class IA) from flecainide (class IC) and their rate-dependent effects.
abstract: The wavelength theory considers two determinants of reentry, i.e., refractoriness and conduction velocity. It does not take excitability into account primarily. We evaluated frequency-dependence of excitability and refractoriness before and after flecainide or procainamide administration in relation to termination of reentrant atrial flutter. After making a Y-shaped lesion in the right atrium, we induced 62 flutters (cycle length 171 +/- 15 ms) by electrical stimulation in 15 pigs. Strength-interval curves were determined to assess excitability and refractoriness. Multiple cycle lengths were used to establish rate-dependent changes. Flutter cycle length increased after flecainide (to 290 +/- 67 ms) or procainamide (to 295 +/- 54 ms). The flutters always terminated abruptly (flecainide dose 103 +/- 104 mg, plasma concentration 370 +/- 21 ng/ml; procainamide dose 1,150 +/- 686 mg, concentration 51 +/- 24 mg/l). Flecainide caused an increase in diastolic thresholds from 0.3 +/- 0.2 to 0.8 +/- 0.5 mA (p < 0.006) and procainamide from 0.5 +/- 0.3 to 0.9 +/- 0.5 mA (p < 0.02). The increase in threshold was frequently dependent. Procainamide increased refractoriness at longer cycle lengths (> or = 250 ms), but this effect was abolished at shorter cycle lengths, indicating that only after significant slowing of the rate, prolongation of refractoriness may appear. Thus, both drugs interrupt reentrant flutter mainly by reducing excitability. Subclassification into IA and IC may be less relevant at high rates. Construction of strength-interval curves and assessment of rate-dependent "postrepolarization refractoriness" should be considered when one studies drugs that influence excitability.
authors.affiliation: Department of Cardiology, University of Groningen, The Netherlands.
authors.forename: H J
authors.initials: HJ
authors.lastname: Crijns
authors.forename: C D
authors.initials: CD
authors.lastname: de Langen
authors.forename: J G
authors.initials: JG
authors.lastname: Grandjean
authors.forename: K J
authors.initials: KJ
authors.lastname: Bel
authors.forename: T
authors.initials: T
authors.lastname: Ebels
authors.forename: K I
authors.initials: KI
authors.lastname: Lie
authors.forename: H
authors.initials: H
authors.lastname: Wesseling
mesh_terms: D000818:Animals; D001282:Atrial Flutter / Q000188:drug therapy* / Q000503:physiopathology; D004562:Electrocardiography / Q000187:drug effects; D005424:Flecainide / Q000627:therapeutic use*; D006329:Heart Conduction System / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D011342:Procainamide / Q000627:therapeutic use*; D013552:Swine; D014261:Tricuspid Valve
chemical_list: D005424:Flecainide; D011342:Procainamide