Wada Y, Satoh K, Taira N
J Cardiovasc Pharmacol. 1984 Sep-Oct;6(5):881-7. doi: 10.1097/00005344-198409000-00022.
We evaluated coronary vasodilator and cardiac effects of PY 108-068 on isolated, blood-perfused sinoatrial (SA) node, atrioventricular (AV) node, and papillary muscle preparations of dogs. PY 108-068 was administered intra-arterially (i.a.). PY 108-068 increased (coronary) blood flow in all preparations. In SA node preparations, the drug produced a decrease in sinus rate and, in large doses, atrial standstill. In AV node preparations, the drug produced an increase in AV conduction time. Large doses caused second- or third-degree AV block, but only when injected into the artery supplying the AV node. The doses producing a 15% (nearly half maximum) decrease in sinus rate or a 15% (nearly half maximum) increase in AV conduction time were two to three times the doses that doubled coronary blood flow. In paced papillary muscle preparations, the drug produced a decrease in the force of contraction. However, the dose required to reduce the force of contraction of the papillary muscle by 50% was about 30 times the dose that doubled coronary blood flow. The drug was entirely ineffective on rate of ventricular automaticity. We conclude that PY 108-068 is not likely to produce reflex tachycardia when administered systemically in coronary vasodilator doses.
我们评估了PY 108 - 068对犬离体、血液灌注的窦房结、房室结及乳头肌标本的冠状血管舒张和心脏效应。PY 108 - 068通过动脉内给药（i.a.）。PY 108 - 068使所有标本中的（冠状）血流量增加。在窦房结标本中，该药物使窦性心率降低，大剂量时可导致心房停搏。在房室结标本中，该药物使房室传导时间延长。大剂量可导致二度或三度房室传导阻滞，但仅在注入供应房室结的动脉时出现。使窦性心率降低15%（接近最大效应的一半）或使房室传导时间延长15%（接近最大效应的一半）的剂量是使冠状血流量加倍的剂量的两到三倍。在起搏乳头肌标本中，该药物使收缩力降低。然而，使乳头肌收缩力降低50%所需的剂量约为使冠状血流量加倍的剂量的30倍。该药物对心室自律性频率完全无效。我们得出结论，当以冠状血管舒张剂量全身给药时，PY 108 - 068不太可能产生反射性心动过速。
