Effects of a novel inotropic agent, BAY y 5959, in conscious dogs: comparison with dobutamine and milrinone.
Effects of a novel inotropic agent, BAY y 5959, in conscious dogs: comparison with dobutamine and milrinone.
复制标题
新型正性肌力药物 BAY y 5959 对清醒狗的影响：与多巴酚丁胺和米力农的比较。
DOI：
10.1152/ajpheart.1997.272.2.h753
复制
发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Vatner,SF
中科院分区：
文献类型：
--
作者：
Sato,N;Uechi,M;Asai,K;Patrick,T;Kudej,RK;Vatner,SF
传统的正性肌力药，例如，那些通过增强的环AMP增加心肌收缩的药物或那些以相对高的O2消耗增加收缩性的药物在临床环境中通常是无用的。因此，已经合成了通过不同机制起作用的较新的药剂。本研究的目的是比较一种新的Ca 2+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条清醒的狗中的作用，长期仪器测量左心室（LV）和动脉压，LV内径，壁厚度，冠状动脉血流量，动脉和冠状窦O2含量。选择等变力剂量的BAY y 5959（20 μ g x kg（-1）x min（-1））、多巴酚丁胺（10 μ g x kg（-1）x min（-1））和米力农（10 μ g x kg（-1）x min（-1）），这些药物使窦性心律时的LV压力发展率较相似基线增加71-78%。多巴酚丁胺（+24 +/- 4%）和米力农（+23 +/- 2%）组心率升高，但BAY y 5959组心率下降（-35 +/- 3%）。多巴酚丁胺使心肌耗氧量（MV（O2））增加88 ± 10%。相比之下，BAY y 5959（+9 +/- 3%）和米力农（+16 +/- 5%; P < 0.05）的MV（O2）增加较少。此外，还通过直接测量心输出量或通过压力-容积环计算机械效率。多巴酚丁胺和米力农没有改变效率;然而，BAY y 5959使效率增加了19 +/-5%。在心率保持不变的情况下，BAY y 5959使MV（O2）增加了32 +/- 4%，但仍使效率增加了28 +/-7%。因此，Ca 2+促进剂BAY y 5959具有独特的特征，这些特征可能是临床应用所需的，其中指示变力性支持，但是增加MV（O2）而不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 O2 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 O2 content. Equi-inotropic doses of BAY y 5959 (20 microg x kg(-1) x min(-1)), dobutamine (10 microg x kg(-1) x min(-1)), and milrinone (10 microg x kg(-1) x min(-1)) 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 +/- 4%) and milrinone (+23 +/- 2%) but fell with BAY y 5959 (-35 +/- 3%). Dobutamine increased myocardial O2 consumption (MV(O2)) by 88 +/- 10%. In contrast, MV(O2) increased less with BAY y 5959 (+9 +/- 3%) and milrinone (+16 +/- 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 +/- 5%. With the heart rate held constant, BAY y 5959 increased MV(O2) by 32 +/- 4% but still increased efficiency by 28 +/- 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 MV(O2) without enhanced mechanical efficiency is deleterious.