Kopia G A, Ohlstein E H, Ruffolo R R
Department of Pharmacology, Smith Kline & French Laboratories, Swedeland, Pennsylvania.
J Pharmacol Exp Ther. 1988 Aug;246(2):434-40.
The relationship between the systemic hemodynamic, inotropic and coronary blood flow actions of the novel inotropic pro-drug, ibopamine, which is the 3,4-diisobutyryl ester derivative of the active form, epinine, was examined in pentobarbital-anesthetized, vagotomized dogs prepared for the recording of systemic arterial blood pressure, heart rate, left ventricular developed pressure and end-diastolic pressure, left ventricular dP/dt, aortic blood flow, left circumflex coronary artery blood flow and lead II ECG. All animals were given i.v. infusions of vehicle followed by 10 min infusions of either epinine (1.1, 3.3, 10 and 30 micrograms/kg/min, n = 4) or ibopamine (3.3, 10, 30 and 100 micrograms/kg/min, n = 4). Both epinine and ibopamine produced dose-dependent increases in mean arterial blood pressure, heart rate, left ventricular developed pressure, left ventricular dP/dt, aortic blood flow, coronary blood flow, left ventricular minute work, stroke work, total peripheral vascular resistance and rate-pressure product. Both epinine and ibopamine decreased coronary vascular resistance, although only the decrease produced by ibopamine achieved statistical significance (P less than .05). Examination of the dose-response curves for epinine and ibopamine showed epinine to be 3- to 4-fold more potent than ibopamine with respect to increasing coronary blood flow, left ventricular stroke work, left ventricular dP/dt and rate-pressure product. However, neither drug increased myocardial work, myocardial oxygen consumption or contractility to a greater extent than the increase in coronary blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)
新型正性肌力前体药物异波帕明(其为活性形式依匹宁的3,4 - 二异丁酰酯衍生物)的全身血流动力学、正性肌力作用及冠状动脉血流作用之间的关系,在戊巴比妥麻醉、迷走神经切断的犬中进行了研究,这些犬用于记录全身动脉血压、心率、左心室舒张末压、左心室压力变化率(dP/dt)、主动脉血流量、左旋冠状动脉血流量及II导联心电图。所有动物先静脉输注溶媒,随后分别静脉输注依匹宁(1.1、3.3、10和30微克/千克/分钟,n = 4)或异波帕明(3.3、10、30和100微克/千克/分钟,n = 4)10分钟。依匹宁和异波帕明均使平均动脉血压、心率、左心室舒张末压、左心室dP/dt、主动脉血流量、冠状动脉血流量、左心室每分钟功、每搏功、总外周血管阻力及速率 - 压力乘积呈剂量依赖性增加。依匹宁和异波帕明均降低冠状动脉血管阻力,不过只有异波帕明产生的降低具有统计学意义(P < 0.05)。对依匹宁和异波帕明剂量 - 反应曲线的研究表明,在增加冠状动脉血流量、左心室每搏功、左心室dP/dt及速率 - 压力乘积方面,依匹宁的效力比异波帕明强3至4倍。然而,两种药物均未使心肌功、心肌氧耗或收缩性增加的程度超过冠状动脉血流量的增加。(摘要截短于250字)