Motomura S, Wu Z J, Hashimoto K
Department of Pharmacology, Yamanashi Medical College, Japan.
Heart Vessels. 1993;8(1):16-22.
Vascular selectivity of lacidipine, a new potent and long-acting coronary vasodilator, was evaluated by a comparison with its negative inotropic, chronotropic, and dromotropic effects in canine isolated, blood-perfused heart preparations. The drug was injected into each nutrient artery in a bolus fashion. In the papillary muscle preparation, the dose causing a 50% increase in blood flow through the anterior septal artery was 0.23 micrograms (mean of five experiments) and the time required for return to half maximum at this dose was 15.0 min even with a bolus injection. Meanwhile, the dose causing a 50% decrease in developed tension of the papillary muscle was 4.6 micrograms. The dose producing a 15% decrease in sinoatrial rate in the sinoatrial node preparation was 8.4 micrograms (n = 5) and that causing a 50% increase in atrio-His interval in the atrioventricular node preparation was 6.8 micrograms (n = 7). These results indicate that the vascular selectivity of lacidipine is markedly high not only against ventricular contractility but also against sinoatrial node automaticity and atrioventricular nodal conduction. The high lipophilicity of lacidipine might be related, at least in part, to its high vascular selectivity, which was equieffective against all the intracardiac variables measured.
通过与拉西地平在犬离体、血液灌注心脏标本中产生的负性肌力、负性变时和负性传导作用进行比较,评估了一种新型强效长效冠状动脉扩张剂拉西地平的血管选择性。该药物以推注方式注入每条营养动脉。在乳头肌标本中,使前间隔动脉血流量增加50%的剂量为0.23微克(五次实验的平均值),即使推注给药,该剂量下恢复到最大血流量一半所需的时间为15.0分钟。同时,使乳头肌收缩张力降低50%的剂量为4.6微克。在窦房结标本中使窦性心率降低15%的剂量为8.4微克(n = 5),在房室结标本中使房室传导间期增加50%的剂量为6.8微克(n = 7)。这些结果表明,拉西地平的血管选择性不仅对心室收缩力明显高,而且对窦房结自律性和房室结传导也明显高。拉西地平的高亲脂性可能至少部分与其高血管选择性有关,它对所测量的所有心内变量具有同等效力。