Hori M, Inoue M, Tamai J, Koretsune Y, Kitakaze M, Iwai K, Ito H, Kitabatake A, Kamada T
Jpn Circ J. 1986 Jan;50(1):37-44. doi: 10.1253/jcj.50.37.
Hemodynamic effects of a new inotropic agent, OPC-8212 (2(1H)-quinolinone derivative) were studied in anesthetized open chest dogs pretreated with propranolol and diltiazem. Three doses (1, 3 and 10 mg/kg) of OPC-8212 were administered intravenously and the net hemodynamic effect (% change) was obtained by subtraction of the effect of the solvent from the gross effect, since the vehicle has a transient, but significant hemodynamic effect. The maximal inotropic effect occurred 3 minutes after administration: LV dP/dt max and cardiac output (CO) increased by 19 +/- 2.5% and 28 +/- 8.5%, respectively, at 3 mg/kg. These cardiotonic effects were dose-dependent, whereas heart rate, peak LV pressure (PLVP) and mean aortic pressure were minimally changed at any dose. Accordingly, systemic vascular resistance (SVR) decreased in a dose-dependent manner although the decrease was much less than that in administration of isoproterenol. The inotropic effect was not blocked by beta-adrenoceptor blockade (propranolol 1 mg/kg), indicating that the cardiotonic action of this agent is not due to beta-adrenergic stimulation. Thus, this agent could reverse beta-blocker-induced heart failure. During infusion of diltiazem (0.1 mg/kg/min following bolus intravenous administration of 0.5 mg/kg), the increases in LV dP/dt max and CO due to OPC-8212 were similar to those in the control study. In contrast to the effects under beta-adrenoceptor blockade, however, decreased PLVP was restored by OPC-8212. Neither chronotropic nor rrhythmogenic effects were observed in the control or with either pharmacological intervention. These results indicate that OPC-8212 has a potent inotropic action with modest vasodilatory effect even with propranolol or diltiazem pretreatment.(ABSTRACT TRUNCATED AT 250 WORDS)
在预先用普萘洛尔和地尔硫䓬处理的麻醉开胸犬中，研究了一种新型强心剂OPC - 8212（2(1H)-喹啉酮衍生物）的血流动力学效应。静脉注射三种剂量（1、3和10 mg/kg）的OPC - 8212，由于溶剂具有短暂但显著的血流动力学效应，通过从总效应中减去溶剂的效应来获得净血流动力学效应（%变化）。给药后3分钟出现最大强心效应：在3 mg/kg时，左心室dp/dt max和心输出量（CO）分别增加19±2.5%和28±8.5%。这些强心作用呈剂量依赖性，而心率、左心室峰值压力（PLVP）和平均主动脉压在任何剂量下变化最小。因此，全身血管阻力（SVR）以剂量依赖性方式降低，尽管降低幅度远小于异丙肾上腺素给药时。β-肾上腺素受体阻断（普萘洛尔1 mg/kg）并未阻断强心效应，表明该药物的强心作用并非由于β-肾上腺素能刺激。因此，该药物可逆转β受体阻滞剂诱发的心力衰竭。在静脉推注0.5 mg/kg后持续输注地尔硫䓬（0.1 mg/kg/min）期间，OPC - 8212引起的左心室dp/dt max和CO增加与对照研究相似。然而，与β-肾上腺素受体阻断下的效应相反，OPC - 8212使降低的PLVP恢复。在对照或任何一种药物干预下均未观察到变时或致心律失常效应。这些结果表明，即使经过普萘洛尔或地尔硫䓬预处理，OPC - 8212仍具有强大的强心作用和适度的血管舒张作用。（摘要截选至250字）
