Millar J S, Vaughan Williams E M
Br J Pharmacol. 1983 Jul;79(3):701-9. doi: 10.1111/j.1476-5381.1983.tb10007.x.
In vitro preparations of rabbit heart were made from which measurements of effective refractory period (ERP), atrio-Hisian (A-H) and His-Purkinje (H-P) conduction times could be obtained, analogous to electrophysiological measurements customarily carried out in vivo. Intracellular potentials also were recorded from the sino-atrial (SA) node, atrium, bundle of His, preterminal Purkinje fibres and papillary muscles. The effects of a range of concentrations of three new antiarrhythmic drugs, melperone, cibenzoline and alinidine were compared, the lower concentrations studied corresponding to clinical levels. At low concentrations the effects of melperone, inducing bradycardia and lengthening ERP, could be attributed to prolongation of action potential duration (APD) in the sinus node and atrial and ventricular tissues. The slope of slow diastolic depolarization was not altered, nor was there any change in A-H or H-P conduction time, or in maximum rate of depolarization (MRD). At higher concentrations melperone had a substantial class 1 action, but there was no negative inotropic effect, or other evidence of restriction of slow inward current. Cibenzoline was primarily a class 1 agent but also lengthened APD to some extent in the SA node and in atrial and ventricular muscle, but not in Purkinje fibres. APD thus became more uniform along the ventricular conducting pathway. Cibenzoline also depressed contractions and increased A-H conduction time, implying restriction of slow inward current. The bradycardia could thus be attributed to a slowing of both depolarization and repolarization in the SA node, without any change in slope of the slow diastolic depolarization. Conduction time was increased in all tissues. 8 Alinidine greatly reduced the slope of the slow diastolic depolarization and slightly lengthened APD in the SA node. MRD was also reduced in the SA node, and A-H conduction time was increased, implying some restriction of slow inward current. However, there was no negative inotropic effect. 9 Alinidine had no significant effect on MRD in atrium, ventricle or Purkinje cells, nor was H-P conduction time altered, implying absence of effect on fast inward current. APD was moderately lengthened in atrium and ventricle but not in Purkinje cells. 10 It was concluded that the effects of the drugs in the sinus node and on ERP and on A-H and H-P conduction times could be accounted for by their selective cellular actions in different regions of the heart.
制备了兔心脏的体外标本，从中可测量有效不应期（ERP）、心房 - 希氏束（A - H）和希氏 - 浦肯野纤维（H - P）传导时间，这类似于通常在体内进行的电生理测量。还从窦房结、心房、希氏束、终末前浦肯野纤维和乳头肌记录了细胞内电位。比较了三种新型抗心律失常药物美哌隆、西苯唑啉和阿利尼丁一系列浓度的作用，所研究的较低浓度对应于临床水平。低浓度时，美哌隆引起心动过缓和延长ERP的作用可归因于窦房结以及心房和心室组织中动作电位持续时间（APD）的延长。舒张期缓慢去极化的斜率未改变，A - H或H - P传导时间以及最大去极化速率（MRD）也没有变化。高浓度时，美哌隆具有明显的Ⅰ类作用，但没有负性肌力作用，也没有其他限制缓慢内向电流的证据。西苯唑啉主要是一种Ⅰ类药物，但在窦房结以及心房和心室肌中也在一定程度上延长了APD，但在浦肯野纤维中没有。因此，沿心室传导通路的APD变得更加均匀。西苯唑啉还抑制收缩并增加A - H传导时间，这意味着限制了缓慢内向电流。因此，心动过缓可归因于窦房结去极化和复极化的减慢，而舒张期缓慢去极化的斜率没有任何变化。所有组织中的传导时间均增加。阿利尼丁大大降低了窦房结中舒张期缓慢去极化的斜率，并略微延长了窦房结中的APD。窦房结中的MRD也降低了，A - H传导时间增加，这意味着对缓慢内向电流有一定限制。然而，没有负性肌力作用。阿利尼丁对心房、心室或浦肯野细胞中的MRD没有显著影响，H - P传导时间也没有改变，这意味着对快速内向电流没有影响。心房和心室中的APD适度延长，但浦肯野细胞中没有。得出的结论是，这些药物在窦房结以及对ERP、A - H和H - P传导时间的作用可由它们在心脏不同区域的选择性细胞作用来解释。
