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氰联吡啶酮的正性肌力作用及其机制的初步探讨 被引量:2

A PRIMARY INVESTIGATION OF MILRINONE'S POSITIVE INOTROPIC EFFECT AND ITS MECHANISM
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摘要 利用心得安制备豚鼠和家兔心衰模型,静注氰联吡啶酮10~15μg/kg,继之以0.5~0.75μg/kg/min恒速静注,可使衰竭心脏Lvdp/dt mex升高约40%,但心率影响不明显。离体豚鼠心室乳头肌和心房实验表明,氰联吡啶酮(0.1~6.4μg/ml)可剂量依赖性地加强心肌收缩力,小剂量(0.1~1.6μg/ml)对心率影响不明显,大剂量时显著加快心率。较高浓度钙离子拮抗剂戊脉安(2×10^(-6)M)可显著减小氰联吡啶酮的正性肌力作用,而β受体阻断剂心得安(5×10^(-7)M)和H_2受体阻断剂西米替丁(5×10^(-3)M)则无此对抗作用。上述结果提示,氰联吡啶酮的正性肌力作用可能也与钙离子经钙通道内流的增加有关,而与β受体、H_2受体无关。 In vivo, intravenous dose of milrinone 10~15μg/kg reversed the hypodynamic parameters of a failing heart induced by propranolol (3~4mg/kg). LVdp/dt max. was increased significantly both in guinea pigs (42±3%, p< 0.01) and rabbits (56±19%, p<0.01) with only slight increase of LVP and almost no change in heart rate.In vitro, very low concentration (0.1~0.8μg/mg) of milrinone increased contractility of isolated guinea pig papillary muscle (14.4±1.9, p<0.05) which was dose related, the threshold concentration of milrinone which increased the atrial rate being about 30 times higher (3.2μg/mg).Our investigation suggest that in addition to phosphodiesterase inhibition, milrinone's positive inotropic effect is due to the increased influx of Ca into myocardial cells via the calcium channel, since pretreatment of papillary muscle with verapamil significantly reduced the inotropic effect of milrinone, but neither propranolol nor cimetidine pretreatment showed such an effect.
出处 《沈阳药学院学报》 CSCD 1993年第3期180-184,共5页
关键词 氰联吡啶酮 正性肌力 心力衰竭 Milrinone Positive inotropic effect Failing heart model Contractility Verapamil Propranolol Cimetidine
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