Hosono M, Satoh K, Taira N
Department of Pharmacology, Tohoku University School of Medicine, Sendai, Japan.
Cardiovasc Drugs Ther. 1988 Jul;2(2):245-53. doi: 10.1007/BF00051241.
The cardiac and coronary vascular effects of T-1583, a selective beta 1-adrenoceptor full agonist, and forskolin, a direct activator of adenylate cyclase, were compared in isolated, blood-perfused papillary muscle, sinoatrial node, and atrioventricular (AV) node preparations of dogs. Both agents were injected intra-arterially. The two agents increased the force of contraction of the paced papillary muscle and the unpaced one, and the rate of automaticity of the latter. They increased sinus rate and accelerated AV nodal conduction. In producing these effects T-1583 was 50 to 80 times more potent than forskolin, indicating that both agents have similar cardiac profiles. At the doses that produced a 50% increase in the force of contraction of the papillary muscle, both agents produced about a 20% increase in sinus rate. Such degrees of force-rate separation were close to those obtained with most new positive inotropic agents with an inhibitory action on cyclic AMP phosphodiesterase. T-1583 differed distinctly from forskolin in that the former increased only slightly coronary blood flow, whereas the latter increased it greatly. Thus, forskolin is more coronary vasodilatory than positively inotropic, and more positively inotropic than positively chronotropic. T-1583 is a more positively inotropic than positively chronotropic and more positively chronotropic than coronary vasodilatory.
在犬离体、血液灌注的乳头肌、窦房结和房室（AV）结标本中，比较了选择性β1肾上腺素能受体完全激动剂T-1583和腺苷酸环化酶直接激活剂福斯高林对心脏和冠状血管的作用。两种药物均经动脉内注射。这两种药物均可增加起搏乳头肌和未起搏乳头肌的收缩力以及后者的自律性。它们可增加窦性心率并加速房室结传导。在产生这些作用时，T-1583的效力比福斯高林强50至80倍，表明这两种药物具有相似的心脏作用模式。在使乳头肌收缩力增加50%的剂量下，两种药物均可使窦性心率增加约20%。这种程度的力-率分离与大多数对环磷酸腺苷磷酸二酯酶有抑制作用的新型正性肌力药物所获得的结果相近。T-1583与福斯高林明显不同，前者仅使冠状动脉血流量略有增加，而后者使其大幅增加。因此，福斯高林的冠状动脉舒张作用强于正性肌力作用，正性肌力作用强于正性变时作用。T-1583的正性肌力作用强于正性变时作用，正性变时作用强于冠状动脉舒张作用。
