NOVEL INOTROPIC AGENT BAY Y 5959 IN CONSCIOUS DOGS: DOBUTAMINE & MILRINONE

传统的正性肌力药，例如，那些增加心肌 通过增强的环AMP或那些增加 在相对高O2成本下的收缩性通常是无用的 在临床环境中。 因此，新的代理人， 通过不同的机制被合成。 的目标 本研究比较了一种新的钙离子促进剂BAY y 5959，与更传统的正性肌力药，多巴酚丁胺和 米力农，在11只清醒的狗中， 测量左心室（LV）和动脉压，LV 内径、壁厚、冠状动脉血流量和动脉 和冠状窦O2含量。 BAY y 5959等变力剂量（20 kg-1.min-1）、多巴酚丁胺（10 g.kg-1.min-1）和米力农（10 kg-1.min-1），使左室压力率增加 窦性心律的发展从相似的基线降低71-78%。 心脏 多巴酚丁胺（+24 q4 %）和米力农（+23 q2 %）的发生率上升，但下降 BAY y 5959（-35 q 3%）。 多巴酚丁胺增加心肌O2 消费量（MV 02）88 q 10%。 相比之下，MV 02随着 BAY y 5959（+9q3%）和米力农（+16q5%; P < 0.05）。 此外，委员会认为， 机械效率也可以直接计算， 测量心输出量或通过压力-容积环。 多巴酚 和米力农没有改变效率;然而，BAY Y 5959增加了 19Q5%。 心率保持不变，BAY y 5959 MVO 2增加了32q4%，但效率仍增加了28q7%。 因此，Ca 2+启动子BAY y 5959具有独特的功能，可能是 对于其中正性肌力支持 指示，但增加了MVO 2，而没有增强机械效率 是有害的

Traditional inotropic agents, e.g., those that increase myocardial contraction through enhanced cyclic AMP or those that increase contractility at a relatively high 02 cost are frequently not useful in the clinical setting. Accordingly, newer agents that operate through different mechanisms have been synthesized. The goal of the present study was to compare the effects of a new Ca2+ promotor, BAY y 5959, with more traditional inotropic agents, dobutamine and milrinone, in 11 conscious dogs chronically instrumented for measurement of left ventricular (LV) and arterial pressures, LV internal diameter, wall thickness, coronary blood flow, and arterial and coronary sinus 02 content. Equi-inotropic doses of BAY y 5959 (20 g.kg-1.min-1), dobutamine (10 g.kg-1.min-1), and milrinone (10 g.kg-1.min1) were selected, which increased the LV rate of pressure development in sinus rhythm by 71-78% from similar baselines. Heart rate rose with dobutamine (+24 q 4%) and milrinone (+23 q 2%) but fell with BAY y 5959 (-35 q 3%). Dobutamine increased myocardial O2 consumption (MV02) by 88 q 10%. In contrast, MV02 increased less with BAY y 5959 (+9 q 3%) and milrinone (+16 q 5%; P < 0.05). Furthermore, mechanical efficiency was also calculated either with direct measurement of cardiac output or by pressure-volume loops. Dobutamine and milrinone did not change efficiency; however, BAY y 5959 increased efficiency by 19 q 5%. With the heart rate held constant, BAY y 5959 increased MVO2 by 32 q 4% but still increased efficiency by 28 q 7%. Thus the Ca2+ promotor BAY y 5959 has unique features that might be desirable for clinical applications where inotropic support is indicated, but increased MVO2 without enhanced mechanical efficiency is deleterious.