Allessie M A, Wijffels M C, Dorland R
Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, The Netherlands.
J Cardiovasc Electrophysiol. 1998 Aug;9(8 Suppl):S69-77.
We recently developed a goat model of sustained atrial fibrillation (AF) in which repetitive induction of AF by burst pacing shortened the atrial effective refractory period (AERP) (electrophysiologic remodeling) and progressively prolonged the paroxysms of AF to become sustained (24 hours) within 1 to 3 weeks (atrial fibrillation begets atrial fibrillation). The aim of the present study was to study the effect of Class I drugs in this animal model of chronic AF.
The effects of hydroquinidine (HQ) on seven chronically fibrillating goats and of flecainide (Fl) on nine goats were studied. Both drugs were infused intravenously until sustained AF was cardioverted or adverse drug effects occurred. HQ and Fl restored sinus rhythm in 86% and 67% of the cases. Adverse drug effects occurred in 14% and 56%, respectively. The average atrial cycle length of AF (AFCL) was prolonged to a different degree. Just before restoration of sinus rhythm, the two drugs had increased AFCL by 72% and 50%. The duration of the QRS complex was prolonged 17% by HQ and 50% by Fl. The RR interval was not affected by HQ and was prolonged slightly by Fl. Directly after restoration of sinus rhythm, the AERP during pacing with an interval of 400 msec was 92 +/- 29 (HQ) and 66 +/- 10 msec (Fl) (control value: 149 +/- 10 msec). Intra-atrial conduction velocity was 83 +/- 7 and 86 +/- 11 cm/sec (control value: 116 +/- 10 cm/sec). Although both drugs were effective in terminating AF, after cardioversion the atrial vulnerability was still very high and a single premature stimulus reinduced AF in 100% of the animals. As a result of the short AERP by the AF-induced remodeling and the depressed intra-atrial conduction by the Class I drugs, directly after cardioversion the atrial wavelength was abnormally short (between 5.7 and 7.5 cm). This explains the still high atrial vulnerability to AF directly after cardioversion by Class I drugs. Surprisingly, the prolongation of AFCL by either Class I drug was not due to lengthening of the functional refractory period but rather to a widening of the excitable gap during AF.
In a goat model of chronic AF, infusion of Class IA and Class IC drugs restored sinus rhythm in 67% to 86% of the cases. However, due to the short AERP and the depressed intra-atrial conduction directly after cardioversion, the atrial vulnerability was still very high and a premature beat easily reinduced AF.
我们最近建立了一种持续性心房颤动（AF）山羊模型，其中通过短阵猝发起搏反复诱发AF可缩短心房有效不应期（AERP）（电生理重构），并在1至3周内使AF发作逐渐延长至持续性（24小时）（房颤引发房颤）。本研究的目的是在这种慢性AF动物模型中研究I类药物的作用。
研究了氢奎尼丁（HQ）对7只慢性颤动山羊和氟卡尼（Fl）对9只山羊的作用。两种药物均静脉输注，直至持续性AF转复或出现药物不良反应。HQ和Fl分别使86%和67%的病例恢复窦性心律。药物不良反应分别发生在14%和56%的病例中。AF的平均心房周期长度（AFCL）有不同程度的延长。在恢复窦性心律前，两种药物使AFCL分别增加了72%和50%。QRS波群时限HQ使其延长了17%，Fl使其延长了50%。RR间期不受HQ影响，Fl使其略有延长。在恢复窦性心律后即刻，以400毫秒间期起搏时的AERP分别为92±29（HQ）和66±10毫秒（Fl）（对照值：149±10毫秒）。心房内传导速度分别为83±7和86±11厘米/秒（对照值：116±10厘米/秒）。虽然两种药物都能有效终止AF，但转复后心房易损性仍然很高，单个期前刺激可使100%的动物再次诱发AF。由于AF诱导的重构使AERP缩短以及I类药物使心房内传导抑制，转复后即刻心房波长异常缩短（5.7至7.5厘米之间）。这解释了I类药物转复后心房对AF仍具有很高易损性的原因。令人惊讶的是，I类药物延长AFCL并非由于功能性不应期延长，而是由于AF期间可兴奋间隙增宽。
在慢性AF山羊模型中，输注IA类和IC类药物可使67%至86%的病例恢复窦性心律。然而，由于转复后AERP缩短和心房内传导抑制，心房易损性仍然很高，一个早搏很容易再次诱发AF。
