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SUSTAINED ATRIAL-FLUTTER AROUND THE TRICUSPID-VALVE IN PIGS - DIFFERENTIATION OF PROCAINAMIDE (CLASS-IA) FROM FLECAINIDE (CLASS-IC) AND THEIR RATE-DEPENDENT EFFECTS

CRIJNS, HJGM., DELANGEN, CDJ., GRANDJEAN, JG., BEL, KJ., EBELS, T., LIE, KI. & WESSELING, H., Mar-1993, In : Journal of Cardiovascular Pharmacology. 21, 3, p. 462-470 9 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • HJGM CRIJNS
  • CDJ DELANGEN
  • JG GRANDJEAN
  • KJ BEL
  • T EBELS
  • KI LIE
  • H WESSELING

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 frequency dependent. Procainamide increased refractoriness at longer cycle lengths (greater-than-or-equal-to 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

Original languageEnglish
Pages (from-to)462-470
Number of pages9
JournalJournal of Cardiovascular Pharmacology
Volume21
Issue number3
Publication statusPublished - Mar-1993

    Keywords

  • ATRIAL FLUTTER, REENTRY, FLECAINIDE, PROCAINAMIDE, PORCINE HEART, SODIUM CHANNEL BLOCKING DRUGS, SINUS RHYTHM, EXCITABLE GAP, CANINE MODEL, MYOCARDIAL-INFARCTION, N-ACETYLPROCAINAMIDE, ACUTE CONVERSION, CONSCIOUS DOGS, FIBRILLATION, QUINIDINE, REENTRY

ID: 6341944