Kobayashi M, Shimotori M, Ogiwara Y, Chiba S
Arch Int Pharmacodyn Ther. 1986 Jan;279(1):72-82.
Our previous study demonstrated that class I antiarrhythmics (fast sodium channel blockers) increased sinoatrial conduction time (SACT) in a dose-related fashion, indicating that a fast sodium current might play an important role in sinoatrial conduction. To assess a role of a slow calcium current in sinoatrial conduction, we examined effects of calcium channel blockers (diltiazem, verapamil, AQ-A 39, dilazep and bepridil) on SACT estimated by the constant atrial pacing in addition to on sinus cycle length (SCL) and on atrial developed tension (DT), using the isolated and blood-perfused dog right atrium. These calcium entry blockers except for bepridil were administered into the cannulated sinus node artery at an infusion rate of 0.2, 0.4 and 1.0 micrograms/min and bepridil at a rate of 0.6, 1.2 and 3.0 micrograms/min. The calcium antagonistic agents produced a dose-dependent decrease in DT and increase in SCL. The observed order of depression of inotropism was verapamil greater than diltiazem greater than bepridil = dilazep greater than AQ-A 39, while the order of negative chronotropism was diltiazem greater than verapamil greater than AQ-A 39 greater than dilazep greater than bepridil. However, as to dromotropism none of the five drugs exerted significant influences on SACT. From the previous and present results it is concluded that the fast sodium current may be predominantly important in sinoatrial conduction.
我们之前的研究表明，I类抗心律失常药（快速钠通道阻滞剂）可使窦房传导时间（SACT）呈剂量依赖性增加，这表明快速钠电流可能在窦房传导中起重要作用。为了评估慢钙电流在窦房传导中的作用，我们使用离体且有血液灌注的犬右心房，研究了钙通道阻滞剂（地尔硫䓬、维拉帕米、AQ - A 39、双嘧达莫和苄普地尔）对通过恒定心房起搏估算的SACT、窦性周期长度（SCL）和心房舒张期张力（DT）的影响。除苄普地尔外，这些钙通道阻滞剂以0.2、0.4和1.0微克/分钟的输注速率注入插管的窦房结动脉，苄普地尔以0.6、1.2和3.0微克/分钟的速率注入。钙拮抗剂使DT呈剂量依赖性降低，SCL增加。观察到的变力作用抑制顺序为维拉帕米＞地尔硫䓬＞苄普地尔 = 双嘧达莫＞AQ - A 39，而负性变时作用顺序为地尔硫䓬＞维拉帕米＞AQ - A 39＞双嘧达莫＞苄普地尔。然而，关于传导性，这五种药物均未对SACT产生显著影响。根据之前和目前的结果得出结论，快速钠电流在窦房传导中可能起主要重要作用。
