Hemodynamic and biochemical effects of a new positive inotropic agent. Antibiotic ionophore RO 2-2985
Hemodynamic and biochemical effects of a new positive inotropic agent. Antibiotic ionophore RO 2-2985
复制标题
新型正性肌力药物的血流动力学和生化作用。
DOI：
10.1161/01.res.40.4.102
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发表时间：
1974
影响因子：
20.1
通讯作者：
M. V. Ray
中科院分区：
文献类型：
--
作者：
A. Schwartz;R. Lewis;H. Hanley;R. Munson;Frederick D. Dial;M. V. Ray
抗生素离子载体RO 2 - 2985（Hoffman-LaRoche; X537A）和A23187（Lilly）使先前结合的钙从分离的肌浆网中突然释放。只有RO 2 - 2985产生了显着抑制钠，钾-腺苷三磷酸酶活性。在麻醉开胸犬中，RO 2 - 2985导致右心室和左心室收缩力、主动脉和冠状动脉流量以及平均中心主动脉血压显著增加，心率发生中度变化，计算的平均外周阻力无变化。单次注射1 mg/kg可使处于诱导休克状态的犬的平均血压从对照组的45 mmHg持续升高至约125 mmHg，持续时间长达7 - 9小时。此时，酪胺引起儿茶酚胺释放，去甲肾上腺素和异丙肾上腺素引起收缩力显著增加。用利血平治疗的狗对药物没有反应。RO 2 - 2985（但不是A23187）在离体兔心房和灌注心室制备物中产生正性肌力作用。RO 2 - 2985在β-受体阻滞后仍产生血压升高。这表明，RO 2 - 2985的作用机制涉及一个非常缓慢的体液物质的释放，通过对特定的钙质子交换的直接影响，或两者兼而有之。据认为，这种药剂具有潜在的治疗应用。
The antibiotic ionophores RO 2-2985 (Hoffman-LaRoche; X537A) and A23187 (Lilly) produced an abrupt release of previously bound calcium from isolated sarcoplasmic reticulum. Only RO 2-2985 produced a significant inhibition of sodium, potassium-adenosinetriphosphatase activity. In anesthetized, open-chest dogs, RO 2-2985 caused a marked increase in right and left ventricular contractile force, aortic and coronary flow, and mean central aortic blood pressure with modest changes in heart rate and no change in calculated mean peripheral resistance. A single injection of 1 mg/kg produced a sustained augmentation of mean blood pressure from a control of 45 mm Hg in dogs that were in induced shock to approximately 125 mm Hg for a period up to 7-9 hours. At that time, tyramine produced a release of catecholamines, and norepinephrine and isoproterenol produced a marked increase in force of contraction. Dogs that were treated with reserpine did not respond to the drug. RO 2-2985, but not A23187, produced positive inotropism in isolated rabbit atrial and perfused ventricular preparations. RO 2-2985 still produced an augmentation in blood pressure after β-receptor blockade. It is suggested that RO 2-2985 acts by a mechanism involving a very slow release of humoral substances, by a direct effect on a specific calcium-proton exchange, or by both. It is thought that this agent has potential therapeutic applications.