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

传统的肌力药，例如那些增加心肌梗死的药物 通过增强的循环AMP或那些增加的收缩 相对较高02成本的伸缩性通常是无用的 在临床环境中。因此，运营的较新的代理 通过不同的机制已被合成。的目标是 本研究旨在比较新型钙离子促进剂Bay Y的作用效果。 5959，与更传统的肌力药、多巴酚丁胺和 米力农，在11只意识清醒的狗身上长期使用 左心室(LV)和动脉压的测量 内径、壁厚、冠脉血流量和动脉 和冠状静脉窦02含量。BAY 5959(20)的均衡性剂量 G·kg~(-1)·min~(-1)、多巴酚丁胺(10 g·kg~(-1)·min~(-1))和米力农(10 G·kg~(-1)·min~(-1))，这增加了LV压力率 在相似基线的基础上，窦性心律的发生率为71%-78%。心 多巴酚丁胺(+24Q4%)和米力农(+23Q2%)的发病率上升，但下降 BAY为5959(-35Q3%)。多巴酚丁胺增加心肌氧分压 消耗(MV02)减少88Q10%。相比之下，MV02的增幅较小 贝Y5959(+9Q3%)和米力农(+16Q5%；P&lt；0.05)。此外， 还计算了机械效率，无论是直接 心输出量的测量或通过压力-容量环。多巴酚丁胺 米力农没有改变效率，但Bay y 5959增加了 效率提高了19Q5%。在心率保持不变的情况下，Bay y 5959 MVO2提高32Q4%，但效率仍提高28Q7%。 因此，钙离子启动子Bay Y 5959具有独特的功能，可能是 适用于肌力支持的临床应用 表明，但增加了MVO2，但没有提高机械效率 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.