Ohyagi A, Sasayama S, Nakamura Y, Lee J D, Kihara Y, Kawai C
Am J Cardiol. 1984 Nov 1;54(8):1108-13. doi: 10.1016/s0002-9149(84)80154-x.
Effect of ICI 118,587 (corwin, ICI), a new cardioselective beta-partial agonist, on left ventricular (LV) function was studied and compared with that of isoproterenol and propranolol in 10 conscious normal dogs, instrumented with a micromanometer and pairs of ultrasonic crystals for analysis of LV wall motion. Heart rate, LV dP/dt and mean circumferential shortening velocity were measured at rest and during 3 levels of treadmill exercise (Ex). Before drug administration (control), the heart rate, dP/dt, percent shortening and mean circumferential shortening velocity were enhanced linearly along with the graded Ex. The Ex response curve shifted upward during isoproterenol infusion and downward after the administration of propranolol. With ICI, hemodynamic and contractile indexes were enhanced at rest as with isoproterenol, while these indexes were depressed during maximal Ex as after propranolol. The Ex response curve after ICI crossed the control response curve at a moderate level of Ex. Thus ICI exerts positive inotropic and chronotropic effects at rest when basal sympathetic tone is low, whereas it exerts negative inotropic and chronotropic properties at maximal Ex when sympathetic tone is high. The inherent dual action of this drug is expected to open a new field of treatment for ischemic heart disease with or without heart failure.
研究了新型心脏选择性β部分激动剂ICI 118,587（科温，ICI）对10只清醒正常犬左心室（LV）功能的影响，并与异丙肾上腺素和普萘洛尔进行了比较。这些犬安装了微测压计和成对的超声晶体，用于分析左心室壁运动。在静息状态和3种跑步机运动（Ex）水平下测量心率、左心室dP/dt和平均圆周缩短速度。在给药前（对照），心率、dP/dt、缩短百分比和平均圆周缩短速度随分级运动呈线性增加。在输注异丙肾上腺素期间，运动反应曲线向上移动，在给予普萘洛尔后向下移动。使用ICI时，静息时的血流动力学和收缩指标与异丙肾上腺素一样增强，而在最大运动时这些指标与普萘洛尔给药后一样降低。ICI给药后的运动反应曲线在中等运动水平时与对照反应曲线相交。因此，当基础交感神经张力较低时，ICI在静息时发挥正性肌力和变时作用，而当交感神经张力较高时，在最大运动时发挥负性肌力和变时作用。预计这种药物固有的双重作用将为伴有或不伴有心力衰竭的缺血性心脏病开辟一个新的治疗领域。
