Direct vasodilator and positive inotropic actions of amrinone.
Direct vasodilator and positive inotropic actions of amrinone.
复制标题
氨力农的直接血管扩张和正性肌力作用。
DOI：
10.1016/0022-2828(80)90022-x
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发表时间：
1980
影响因子：
5
通讯作者：
Schwartz,A
中科院分区：
文献类型：
--
作者：
Millard,RW;Dubé,G;Grupp,G;Grupp,I;Alousi,A;Schwartz,A
最近，一种新的正性肌力药物已被临床试验用于治疗难治性充血性心力衰竭[3，8]。该化合物具有联吡啶结构。氨力农已被证明在离体心脏组织的变力状态中产生剂量依赖性增加[I，2，51，并且在某些方面被比作洋地黄。尽管快速应用于人类心力衰竭，但作用机制仍有待确定。它似乎不影响Na-K-ATP酶、哇巴因与Na-K-ATP酶、腺苷酸环化酶、肌浆网或线粒体的结合，也不刺激$-肾上腺素能受体或影响心肌中环AMP的水平[Z，91.氨力农除具有强心作用外，还能适度降低动脉血压和全身血管阻力，本文报道了在离体组织和完整动物标本中，氨力农的血管活性与强心作用的关系。具体而言，这些研究旨在确定氨力农对（1）大鼠、豚鼠和犬的心房和心室收缩力，（2）猪冠状动脉、肾动脉和股动脉条的收缩力，（3）清醒和麻醉犬的局部心肌缩短和力，以及（4）犬的总冠状动脉流量和局部冠状动脉流量的影响和可能的作用机制。从大鼠（a = 10）、豚鼠（n = 14）和犬（a = 4）获得心房和心室（乳头肌和小梁肌）的条，这些条分别用50、25和25 mg/kg戊巴比妥钠肝素化和麻醉。取出心脏，立即悬挂并通过Langendorf装置灌注。然后解剖心房和乳头肌条，并固定在70 ml Krebs-Henseleit溶液中，该溶液含有118 mM NaCl、4.7 mM KCl、2.5 mM CaCl、1.2 mM MgSO、1.2 mM KH、PO、0.5 mM CaEDTA、25 mM NaHCO和5.5 mM葡萄糖。将溶液用95 ° C的CO2和596 ° C的CO2饱和，并在37 ℃下调节至pH7.4.所有心肌组织均在等长条件下进行研究，初始负荷为1 g *。没有组织表现出自发活动，所有组织均以2 Hz，持续时间0.5 ms，阈值电压为2倍进行刺激。在累积基础上获得剂量反应曲线。所有心脏条对CaCl和异丙肾上腺素（1 × 10 - 8M）激发反应正常。在研究的三个物种中，值得注意的是，只有大鼠对氨力农无反应（表1）。在豚鼠中，
Recently a new inotropic agent has been tested clinically for the treatment of refractory congestive heart failure [3, 8]. The compound has a bipyridine structure. Amrinone has been demonstrated to produce dose-dependent increases in the inotropic state of isolated cardiac tissues [I, 2, 51, and in some ways has been likened to digitalis. Despite the rapid application to human heart failure, the mechanism of action remains to be identified. It does not appear to affect Na-K-ATPase, ouabain binding to Na-K-ATPase, adenylate cyclase, sarcoplasmic reticulum, or mitochondria, nor does it stimulate $-adrenergic receptors or affect levels of cyclic AMP in heart muscle [Z, 91. In addition to its cardiac inotropic ‘action, Amrinone also produces moderate decreases in arterial blood pressure and systemic vascular resistance.The studies reported here attempt to relate the vasoactive with the inotropic actions in both isolated tissues and in intact, whole animal preparations. Specifically, the studies were designed to determine the effect and possible mechanisms of action of Amrinone on (1) contractile force of atria and ventricles of rat, guineapig and dog,(2) contractile force of pig coronary, renal and femoral artery strips,(3) regional myocardial shortening and force in conscious and anesthetized dogs, and (4) total and regional coronary flow in dogs. Strips of atria and ventricles (papillary and trabecular muscles) were obtained from rat (a= lo), guinea-pig(n= 14) and dog (a= 4) which were heparinized and anesthetized with pentobarbital sodium, 50, 25 and 25 mg/kg, respectively. Hearts were removed and immediately suspended and perfused by a Langendorf apparatus. Atria and papillary strips were then dissected and mounted in 70 ml Krebs-Henseleit solution containing 118 mM NaCl, 4.7 mM KCI, 2.5 mM CaCl,, 1.2 mM MgSO,, 1.2 mM KH, PO,, 0.5 mM CaEDTA, 25 mM NaHCO,, and 5.5 mM glucose. The solution was saturated with 95” & 0, and 596 CO, and adjusted to a pH” of 7.4 at 37 C. All myocardial tissues were studied under isometric conditions with an initial load of 1 g*. No tissues exhibited spontaneous activity and all were stimulated at 2 Hz, duration 0.5 ms with twice threshhold voltage. Dose response curves were obtained on a cumulative basis. All cardiac strips responded normally to challenges with CaCl, and iso-1) roterenol (1 x 10-s M). Of the three species studied, it was of interest that only he rat failed to respond to Amrinone(Table 1). In guinea-pig similar sensitivity