Patterson E, Scherlag B J, Berlin K D, Lazzara R
Department of Pharmacology, University of Oklahoma Health Sciences Center, Oklahoma City.
J Pharmacol Exp Ther. 1991 Nov;259(2):558-65.
To obtain a better understanding of the possible electrophysiological bases of the antiarrhythmic actions of 7-benzyl-3-thia-7-azabicyclo[3.3.1]nonane hydroperchlorate (BRB-I-28), microelectrode recordings of myocardial electrical activity were obtained in canine Purkinje and ventricular tissue, and in isolated canine ventricular myocytes. BRB-I-28 (1.0 and 3.2 mg/l) reduced Vmax, action potential amplitude, overshoot potential and conduction velocity in Purkinje tissues without altering action potential duration or spontaneous automaticity. Vmax and conduction velocity were reduced only at paced cycle lengths of 500 msec or less. BRB-I-28 (3.2 and 10 mg/l) also reduced Vmax, action potential amplitude and overshoot potential in subendocardial and epicardial ventricular muscle, with Vmax reduced only at cycle lengths of 500 msec or less. Recovery half-times for Vmax estimated in canine subendocardium were 330 +/- 28 and 336 +/- 25 msec at BRB-I-28 concentrations of 3.2 and 10 mg/l, respectively. In epicardium, conduction velocity longitudinal to fiber orientation was depressed more than conduction velocity transverse to fiber orientation, despite similar changes in Vmax. In both epicardial and subendocardial ventricular muscle, a reduction in Vmax is observed in the absence of alterations in action potential duration. Experiments using myocytes isolated from canine epicardial tissue demonstrated similar rate-dependent changes in Vmax as ventricular epicardium. The data demonstrate a rate-dependent depression of Vmax by BRB-I-28 in canine ventricular tissues. The depression of conduction occurs only at rapid paced rates and occurs in the absence of changes in Purkinje cell automaticity or action potential duration.(ABSTRACT TRUNCATED AT 250 WORDS)
为了更好地理解高氯酸7-苄基-3-硫杂-7-氮杂双环[3.3.1]壬烷（BRB-I-28）抗心律失常作用的可能电生理基础，在犬浦肯野纤维和心室组织以及分离的犬心室肌细胞中进行了心肌电活动的微电极记录。BRB-I-28（1.0和3.2mg/L）降低了浦肯野组织中的最大上升速率（Vmax）、动作电位幅度、超射电位和传导速度，而不改变动作电位持续时间或自发自律性。仅在起搏周期长度为500毫秒或更短时，Vmax和传导速度才降低。BRB-I-28（3.2和10mg/L）也降低了心内膜下和心外膜心室肌中的Vmax、动作电位幅度和超射电位，仅在周期长度为500毫秒或更短时Vmax降低。在BRB-I-28浓度分别为3.2和10mg/L时，犬心内膜下Vmax的恢复半衰期分别为330±28和336±25毫秒。在心外膜中，尽管Vmax有类似变化，但纵向于纤维方向的传导速度比横向于纤维方向的传导速度降低更明显。在心外膜和心内膜下心室肌中，在动作电位持续时间无改变的情况下均观察到Vmax降低。使用从犬心外膜组织分离出的心机细胞进行的实验表明，Vmax存在与心室心外膜类似的速率依赖性变化。数据表明BRB-I-28在犬心室组织中对Vmax有速率依赖性抑制作用。传导抑制仅发生在快速起搏速率时，且发生时浦肯野细胞自律性或动作电位持续时间无变化。（摘要截短于250字）
