Le Grand B, Le Heuzey J Y, Perier P, Peronneau P, Lavergne T, Hatem S, Guize L
U 256 INSERM, Instrumentation et Dynamique Cardiovasculaire, Hôpital Broussais, Paris.
Cardiovasc Res. 1990 Mar;24(3):232-8. doi: 10.1093/cvr/24.3.232.
The aim of the study was to examine the electrophysiological characteristics of human atrial specimens collected during heart surgery and to investigate the effects of the class I antiarrhythmic agent flecainide on their electrical activity.
Atrial specimens were studied using standard microelectrode techniques, with and without superfused flecainide (5 x 10(-7) M) or the transient outward current inhibitor 4-aminopyridine (0.5 mM).
Atrial fragments 0.5-1.0 cm2 were obtained at operation from 34 patients, mean age 30 years. There was no history of previous atrial arrhythmia in any patient and drug therapy was stopped 24 h before surgery.
Two types of transmembrane action potential were identified: (1) triangular shaped potentials (group A, classically found in animal models); (2) potentials with a large plateau preceded by a notch (group B). The effect of flecainide was compared on the the two types of action potential. In both, flecainide lessened the depolarisation rate. In group B, but not in group A, it increased the action potential duration at 50% and 90% repolarisation (APD50, APD90) and the effective refractory period. The notch in group B action potentials is generated by transient outward currents (Ito). Inhibition of these currents, either by increasing the pacing rate or by adding 4-aminopyridine, limited the increase in APD50, APD90, and effective refractory period generated by the presence of flecainide.
The effects of flecainide on the atrial repolarisation process depend on the shape of the action potential. These effects are more marked in cells with a plateau, where Ito is activated.
本研究旨在检测心脏手术期间采集的人心房标本的电生理特性,并研究Ⅰ类抗心律失常药物氟卡尼对其电活动的影响。
采用标准微电极技术研究心房标本,分别在有和没有超灌流氟卡尼(5×10⁻⁷ M)或瞬时外向电流抑制剂4-氨基吡啶(0.5 mM)的情况下进行。
在手术中从34例患者获取0.5 - 1.0 cm²的心房碎片,患者平均年龄30岁。所有患者既往均无房性心律失常病史,术前24小时停用药物治疗。
识别出两种跨膜动作电位类型:(1)三角形电位(A组,典型见于动物模型);(2)有切迹且前面有大平台期的电位(B组)。比较了氟卡尼对这两种动作电位类型的影响。在两种类型中,氟卡尼均降低了去极化速率。在B组而非A组中,它增加了复极化50%和90%时的动作电位时程(APD50、APD90)以及有效不应期。B组动作电位的切迹由瞬时外向电流(Ito)产生。通过增加起搏频率或添加4-氨基吡啶抑制这些电流,可限制氟卡尼存在时APD50、APD90和有效不应期的增加。
氟卡尼对心房复极化过程的影响取决于动作电位的形状。在有平台期且Ito被激活的细胞中,这些影响更为显著。