Effects of MDL 19205 (piroximone), a new cardiotonic agent, on electrophysiological, mechanical, and intracellular ionic characteristics of sheep cardiac tissues.
Effects of MDL 19205 (piroximone), a new cardiotonic agent, on electrophysiological, mechanical, and intracellular ionic characteristics of sheep cardiac tissues.
复制标题
新型强心剂 MDL 19205（吡罗昔酮）对绵羊心脏组织的电生理、机械和细胞内离子特性的影响。
DOI：
10.1097/00005344-198605000-00024
复制
发表时间：
1986
影响因子：
3
通讯作者：
Wasserstrom,JA
中科院分区：
文献类型：
--
作者：
Wasserstrom,JA
本研究旨在表征 MDL 19205（一种新型强效非糖苷正性肌力药物）的心脏电生理和机械效应。此外，还测量了细胞内 Na+ 活性 (ana)，以确定该药物是否可以通过增加 ana 以及其次通过 Na+-Ca2+ 交换增加细胞内钙来产生正性肌力作用。实验是在从绵羊心脏获得的自由运行的小梁肌和浦肯野纤维中进行的。以下是 MDL 19205 最显着的作用：(a) 心室和浦肯野组织中的动作电位持续时间减少：(b) 心室肌收缩力的累积剂量依赖性增加，但浦肯野束中的收缩力没有增加：(c) 浦肯野纤维中的 aNa 没有变化，伴随着该药物的正性肌力作用；(d) 在 β-肾上腺素能阻滞存在的情况下，剂量反应关系变化四倍与索他洛尔 (10-7 M) 一起使用；(e) 增强浦肯野纤维的舒张去极化，从而导致因过度驱动而加速的自动性：以及 (f) 8-溴-cAMP (1 mM) 增强 MDL 19205 的正性肌力作用，表明 MDL 19205 具有有效的磷酸二酯酶抑制作用。这些结果表明 MDL 19205 至少发挥其正性肌力和自动作用的一部分是通过刺激β-肾上腺素能受体来实现的。这种作用与其抑制磷酸二酯酶的能力一起发生，从而促进心肌细胞中 cAMP 的积累。其他细胞内作用也可能有助于该药物的作用，但它们不依赖于 aNa 的增加或动作电位平台或持续时间的显着变化。
This study was undertaken to characterize the cardiac electrophysiological and mechanical effects of MDL 19205, a new and potent nonglycoside, positive inotropic agent. In addition, intracellular Na+ activity (ana) was measured to determine if this agent might produce its inotropic effects by increasing ana and secondarily by increasing intracellular calcium via Na+-Ca2+ exchange. Experiments were conducted in free-running trabecular muscles and Purkinje fibers obtained from sheep hearts. The following were the most significant effects of MDL 19205:(a) a decrease in action potential duration in both ventricular and Purkinje tissues:(b) a cumulative dose-dependent increase in contractile force in ventricular muscle but not in Purkinje strands:(c) no change in aNa in Purkinje fibers to accompany the positive inotropic effect of this agent;(d) a shift in the doseresponse relation by fourfold in the presence of [beta]-adrenergic blockade with sotalol (10-7 M);(e) an enhancement of diastolic depolarization in Purkinje fibers resulting in automaticity that is accelerated by overdrive: and (f) a potentiation of the positive inotropic effects of MDL 19205 by 8-bromo-cAMP (1 mM), indicating a potent phosphodiesterase inhibitory action of MDL 19205. These results suggest that MDL 19205 exerts at least part of its positive inotropic and automatic actions through stimulation of [beta]-adrenergic receptors. This action occurs in conjunction with its ability to inhibit phosphodies-terase, thus promoting an accumulation-of cAMP in cardiac cells. Other intracellular actions may also contribute to the effect of this drug, but they do not rely on an increase in aNa or dramatic changes in the action potential plateau or duration.