Crijns H J, de Langen C D, Grandjean J G, Bel K J, Ebels T, Lie K I, Wesseling H
Department of Cardiology, University of Groningen, The Netherlands.
J Cardiovasc Pharmacol. 1993 Mar;21(3):462-70. doi: 10.1097/00005344-199303000-00017.
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.
波长理论考虑了折返的两个决定因素，即不应期和传导速度。它主要没有考虑兴奋性。我们评估了氟卡尼或普鲁卡因胺给药前后兴奋性和不应期的频率依赖性与折返性房扑终止的关系。在右心房制作Y形损伤后，我们通过电刺激在15头猪中诱发了62次房扑（周期长度171±15毫秒）。测定强度-间期曲线以评估兴奋性和不应期。使用多个周期长度来确定速率依赖性变化。氟卡尼（增至290±67毫秒）或普鲁卡因胺（增至295±54毫秒）给药后房扑周期长度增加。房扑总是突然终止（氟卡尼剂量103±104毫克，血浆浓度370±21纳克/毫升；普鲁卡因胺剂量1150±686毫克，浓度51±24毫克/升）。氟卡尼使舒张期阈值从0.3±0.2毫安增加到0.8±0.5毫安（p<0.006），普鲁卡因胺使舒张期阈值从0.5±0.3毫安增加到0.9±0.5毫安（p<0.02）。阈值的增加通常具有频率依赖性。普鲁卡因胺在较长周期长度（≥250毫秒）时增加不应期，但在较短周期长度时这种作用消失，这表明只有在心率显著减慢后，不应期延长才可能出现。因此，两种药物主要通过降低兴奋性来中断折返性房扑。在高心率时，分为IA类和IC类可能不太相关。当研究影响兴奋性的药物时，应考虑构建强度-间期曲线和评估速率依赖性的“复极后不应期”。
