Scriabine A, Van Arman C G, Morgan G, Morris A A, Bennett C D, Bohidar N R
J Cardiovasc Pharmacol. 1979 Sep-Oct;1(5):571-83. doi: 10.1097/00005344-197909000-00009.
The positive inotropic effect of anthopleurin-A (AP-A) was studied in vitro on isolated cat heart papillary muscles and in vivo in anesthetized and conscious dogs. In vitro, in low Ca2+ solution (1.27 mM), AP-A increased the force of contractions of isolated cat heart papillary muscles at concentrations from 0.2 x 10(-8) M and higher; on a molar basis, AP-A was more than 200 times as potent as digoxin and on a weight basis, 33 times as potent. In vivo in anesthetized dogs, AP-A at 0.2 microgram/kg/min i.v. increased myocardial contractile force; the geometric mean dose of AP-A required to increase the contractile force by 25% was 2.6 micrograms/kg; the corresponding dose of digoxin (infused at 2.8 micrograms/kg/min) was 107.4 micrograms/kg. The geometric mean lethal dose of AP-A for 8 dogs was 19.3 and that of digoxin 263.2 micrograms/kg i.v. The therapeutic index of AP-A was significantly higher than that of digoxin. All animals that received either AP-A or digoxin died in ventricular fibrillation. The reversal of t-wave was typical for AP-A. As measured by left ventricular pressure telemetry, AP-A, 2 micrograms/kg i.v. single dose, increased LV dp/dt max in conscious dogs for longer than 2 hr.
在体外，对分离的猫心脏乳头肌以及在体内对麻醉和清醒犬研究了海葵毒素-A（AP-A）的正性肌力作用。在体外，在低钙溶液（1.27 mM）中，AP-A在浓度为0.2×10⁻⁸ M及更高时可增加分离的猫心脏乳头肌的收缩力；以摩尔计，AP-A的效力比地高辛强200倍以上，以重量计则强33倍。在体内，在麻醉犬中，静脉注射AP-A 0.2微克/千克/分钟可增加心肌收缩力；使收缩力增加25%所需的AP-A几何平均剂量为2.6微克/千克；地高辛（以2.8微克/千克/分钟输注）的相应剂量为107.4微克/千克。8只犬静脉注射AP-A的几何平均致死剂量为19.3，地高辛为263.2微克/千克。AP-A的治疗指数显著高于地高辛。接受AP-A或地高辛的所有动物均死于心室颤动。T波倒置是AP-A的典型表现。通过左心室压力遥测测量，静脉注射单剂量2微克/千克的AP-A可使清醒犬的左心室dp/dt max增加超过2小时。
