Narimatsu A, Taira N
Naunyn Schmiedebergs Arch Pharmacol. 1976 Aug;294(2):169-77. doi: 10.1007/BF00507850.
The effects on atrio-ventricular (A-V) conduction and blood flow of calcium-antagonists (verapamil, nifedipine and diltiazem), local anaesthetics (procaine and lidocaine) and quinidine were investigated in the isolated, cross-circulated A-V node preparation of the dog. The drugs were injected individually into the posterior septal artery (PSA) through which the upper part of the A-V node is mainly perfused or into the anterior septal artery (ASA) through which the lower part of the node and the more distal conduction system are perfused. Single injections into the PSA of nifedipine (0.3-10 mug), verapamil (1-30 mug), diltiazem (1-30 mug), quinidine (30-300 mug), lidocaine (100 mug-1 mg) and procaine (300 mug-3 mg) produced a dose-related increase in the A-V conduction time and with higher doses of these drugs a second or third degree block of A-V conduction occurred. Nifedipine (0.3-30 mug) and verapamil (1-100 mug) injected into the ASA scarcely affected A-V conduction. Quinidine (30 mug-1 mg) and lidocaine (100 mug-3 mg) injected into the ASA prolonged the A-V conduction time in a dose-related manner, although the effects were less prominent than those produced upon injection into the PSA. High doses of quinidine (3 mg) and lidocaine (3-10 mg) injected into the ASA altered the shape of ventricular bipolar electrograms and prolonged the time interval between an electrogram of the right bundle branch and that of the ventricle. The results are consistent with the hypothesis that in excitation of A-V nodal cells a slow calcium current rather than a fast sodium current plays an important role and that in the His-Purkinje-ventricular system the fast sodium current is predominant. Single injections of the 6 drugs into the PSA produced a dose-related increase in blood flow through the PSA. All drugs but nifedipine increased the blood flow in almost the same dose range that caused impairment of A-V conduction. Nifedipine was 10 times more potent in increasing the blood flow than in impairing A-V conduction.
在犬的离体交叉循环房室结标本中，研究了钙拮抗剂（维拉帕米、硝苯地平、地尔硫䓬）、局部麻醉药（普鲁卡因、利多卡因）和奎尼丁对房室传导及血流的影响。将这些药物分别注入后间隔动脉（PSA）或前间隔动脉（ASA），PSA主要为房室结上部供血，ASA为房室结下部及更远端的传导系统供血。单次向后间隔动脉注入硝苯地平（0.3 - 10微克）、维拉帕米（1 - 30微克）、地尔硫䓬（1 - 30微克）、奎尼丁（30 - 300微克）、利多卡因（100微克 - 1毫克）和普鲁卡因（300微克 - 3毫克），可使房室传导时间呈剂量依赖性增加，且这些药物剂量较高时会出现二度或三度房室传导阻滞。注入前间隔动脉的硝苯地平（0.3 - 30微克）和维拉帕米（1 - 100微克）对房室传导几乎无影响。注入前间隔动脉的奎尼丁（30微克 - 1毫克）和利多卡因（100微克 - 3毫克）可使房室传导时间呈剂量依赖性延长，不过其作用不如注入后间隔动脉时显著。注入前间隔动脉的高剂量奎尼丁（3毫克）和利多卡因（3 - 10毫克）可改变心室双极电图的形态，并延长右束支电图与心室电图之间的时间间隔。这些结果与以下假说相符：在房室结细胞兴奋过程中，慢钙电流而非快钠电流起重要作用；在希氏 - 浦肯野 - 心室系统中，快钠电流占主导。将这6种药物单次注入后间隔动脉，可使后间隔动脉的血流呈剂量依赖性增加。除硝苯地平外，所有药物在导致房室传导受损的几乎相同剂量范围内均可增加血流。硝苯地平增加血流的效力比损害房室传导的效力高10倍。
