Imanaga I, Kaneda T, Miyakawa N
Nihon Yakurigaku Zasshi. 1979 Mar;75(2):147-57. doi: 10.1254/fpj.75.147.
The effects of dobutamine on inotropism and chronotropism of the heart were studied in vivo and in vitro and were compared with those of dopamine and isoproterenol. These compounds increased epicardial contractile force and the heart rate of the open-chest, bilaterally vagotomized dog under pentobarbital anesthesia. The dose-ratio for the contraction was [dobutamine: dopamine: isoproterenol = 1:0.8:40] and for the heart rate, [= 1:1:300]. Both drugs augmented the twitch contraction of the isolated dog ventricular papillary muscle with the dose-ratio of [dobutamine: dopamine: isoproterenol = 1:0.7:11]. This mechanical response was associated with an elevation of the plateu voltage and an increase in repolarization of the action potential, but with no alteration of the maximum rate of rise of the action potential, the resting potential and the input membrane resistance. The discharge frequency of the rabbit S-A node pacemaker potential was accelerated chiefly due to an increase in the slope of the diastolic slow depolarization. With concentration of these catecholamines for the equivalent positive inotropic potency on the papillary muscle, this effect of isoproterenol was more potent than the effects of dobutamine and dopamine. These positive inotropic and chronotropic actions of the catecholamines were abolished by a beta-receptor antagonist. Those actions of dopamine were markedly reduced by reserpine pretreatment. In addition, dobutamine had little vascular effect. These results indicatte that dobutamine has a positive inotropic effect and a less positive chronotropic effect and that such is due to the direct action on the ventricular myocardium and the S-A node through beta 1-adrenergic receptors.
在体内和体外研究了多巴酚丁胺对心脏变力性和变时性的影响,并与多巴胺和异丙肾上腺素进行了比较。这些化合物可增加戊巴比妥麻醉下开胸、双侧迷走神经切断犬的心外膜收缩力和心率。收缩的剂量比为[多巴酚丁胺:多巴胺:异丙肾上腺素 = 1:0.8:40],心率的剂量比为[= 1:1:300]。两种药物均能增强离体犬心室乳头肌的抽搐收缩,剂量比为[多巴酚丁胺:多巴胺:异丙肾上腺素 = 1:0.7:11]。这种机械反应与平台期电压升高和动作电位复极化增加有关,但动作电位的最大上升速率、静息电位和输入膜电阻无改变。兔窦房结起搏电位的放电频率主要由于舒张期缓慢去极化斜率增加而加快。在乳头肌上,当这些儿茶酚胺的浓度产生等效的正性肌力作用时,异丙肾上腺素的这种作用比多巴酚丁胺和多巴胺的作用更强。这些儿茶酚胺的正性肌力和变时作用被β受体拮抗剂所消除。多巴胺的这些作用在利血平预处理后明显减弱。此外,多巴酚丁胺对血管的作用很小。这些结果表明,多巴酚丁胺具有正性肌力作用和较弱的正性变时作用,这是由于它通过β1肾上腺素能受体直接作用于心室心肌和窦房结。