Vatner S F, McRitchie R J, Braunwald E
J Clin Invest. 1974 May;53(5):1265-73. doi: 10.1172/JCI107673.
The effects of dobutamine ([+/-]-4-[2-[[3-(p-hydroxyphenyl)-1-methyl propyl] amino] ethyl] pyrocatechol hydrochloride), a new synthetic cardioactive sympathomimetic amine, were examined on direct and continuous measurements of left ventricular (LV) diameter (D), pressures (P), velocity of shortening (V), dP/dt, dP/dt/P, arterial pressure, cardiac output, and regional blood flows in the left circumflex coronary, mesenteric, renal, and iliac beds in healthy, conscious dogs. At the highest dose of dobutamine examined, 40 mug/kg/min, the drug increased dP/dt/P from 65+/-3 to 128+/-4 s(-1) and isolength velocity from 72+/-4 to 120+/-7 mm/s without affecting LV end diastolic D significantly. Mean arterial P rose from 92+/-2 to 104+/-3 mm Hg and heart rate from 78+/-3 to 111+/-7 beats/min, while LV end systolic D fell from 24.1+/-1.4 to 19.9+/-1.8 mm, reflecting a rise in stroke volume from 30+/-4 to 42+/-3 ml. Cardiac output rose from 2.41+/-0.23 to 4.35+/-0.28 liter/min, while calculated total peripheral resistance declined from 0.042+/-0.005 to 0.028+/-0.003 mm Hg/ml/min. The greatest increases in flow and decreases in calculated resistance occurred in the iliac and coronary beds, and the least occurred in the renal bed. Propranolol blocked the inotropic and beta(2) dilator responses while vasoconstricting effects mediated by alpha adrenergic stimulation remained in each of the beds studied. When dobutamine was infused after a combination of practolol and phentolamine, dilatation occurred in each of the beds studied. These observations indicate that dobutamine is a potent positive inotropic agent with relatively slight effects on preload, afterload, or heart rate, and thus may be a potentially useful clinical agent. The one property of this drug which is not ideal is its tendency to cause a redistribution of cardiac output favoring the muscular beds at the expense of the kidney and visceral beds.
研究了新型合成的具有心脏活性的拟交感胺多巴酚丁胺([±]-4-[2-[[3-(对羟基苯基)-1-甲基丙基]氨基]乙基]邻苯二酚盐酸盐)对健康清醒犬左心室(LV)直径(D)、压力(P)、缩短速度(V)、dP/dt、dP/dt/P、动脉压、心输出量以及左旋支冠状动脉、肠系膜、肾和髂血管床局部血流量的直接连续测量值的影响。在所研究的多巴酚丁胺最高剂量40μg/kg/min时,该药使dP/dt/P从65±3增至128±4 s⁻¹,等长速度从72±4增至120±7 mm/s,而未显著影响左心室舒张末期直径。平均动脉压从92±2升至104±3 mmHg,心率从78±3升至111±7次/分钟,而左心室收缩末期直径从24.1±1.4降至19.9±1.8 mm,反映出每搏输出量从30±4增至42±3 ml。心输出量从2.41±0.23升至4.35±0.28升/分钟,而计算出的总外周阻力从0.042±0.005降至0.028±0.003 mmHg/ml/min。血流量增加最大且计算出的阻力降低最大的发生在髂血管床和冠状动脉床,而最小的发生在肾血管床。普萘洛尔阻断了正性肌力作用和β₂舒张反应,而在所研究的每个血管床中,由α肾上腺素能刺激介导的血管收缩作用依然存在。当在普萘洛尔和酚妥拉明联合使用后输注多巴酚丁胺时,在所研究的每个血管床中均出现了扩张。这些观察结果表明,多巴酚丁胺是一种强效正性肌力药物,对前负荷、后负荷或心率的影响相对较小,因此可能是一种潜在有用的临床药物。该药物的一个不理想特性是其倾向于导致心输出量重新分布,有利于肌肉血管床,而以肾血管床和内脏血管床为代价。