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异波帕明对全身、肺和局部血流动力学的影响。在麻醉犬身上进行的实验研究。

Effects of ibopamine on systemic, pulmonary and regional hemodynamics. Experimental investigations in anesthetized dogs.

作者信息

Merlo L, Ghirardi P, Brusoni B, Mussini E, Marchetti G

出版信息

Arzneimittelforschung. 1986 Feb;36(2A):304-11.

PMID:3707641
Abstract

The effects of a new orally effective dopamine-like derivative, ibopamine (SB-7505), the 3,4-diisobutyryl ester of N-methyldopamine, on the cardiovascular system were investigated in anesthetized dogs. Ibopamine increased dose-dependently stroke volume index, cardiac index, left ventricular pressure, its first derivative: dP/dt, peak velocity left ventricular ejection and renal blood flow. After beta-blockade the positive inotropic effect of ibopamine is inhibited. Total peripheral resistance and renal vascular resistance decreased after ibopamine. Urine output was increased dose-dependently, reaching 115% after ibopamine 8 mg/kg intraduodenally. Coronary and femoral flows and resistance did not change after administration of 4 and 8 mg/kg. Only very high doses (24 mg/kg) caused an increase in flow and resistance. Mesenteric flow decreased transiently and then returned to the previous level or increased considerably over the basal figures when a high dose was used. No significant changes or fall in heart rate were observed with doses up to 16 mg/kg and no significant changes in pulmonary resistance were noted. The data obtained from the present investigation show, however, that oral ibopamine is capable of producing most of the effects induced by intravenously given dopamine in anesthetized dogs. Ibopamine's cardiac and renal effects may open new prospects for the long-term treatment of chronic heart failure in human subjects.

摘要

研究了一种新型口服有效的多巴胺样衍生物异波帕明(SB - 7505),即N - 甲基多巴胺的3,4 - 二异丁酯,对麻醉犬心血管系统的影响。异波帕明可使每搏量指数、心脏指数、左心室压力、其一阶导数:dP/dt、左心室射血峰值速度和肾血流量呈剂量依赖性增加。β受体阻断后,异波帕明的正性肌力作用受到抑制。异波帕明给药后,总外周阻力和肾血管阻力降低。尿量呈剂量依赖性增加,十二指肠内给予8mg/kg异波帕明后尿量增加至115%。给予4mg/kg和8mg/kg后,冠状动脉和股动脉血流量及阻力未发生变化。只有非常高的剂量(24mg/kg)才会导致血流量和阻力增加。使用高剂量时,肠系膜血流量短暂减少,然后恢复到先前水平或比基础值大幅增加。给予高达16mg/kg的剂量时,未观察到心率有显著变化或下降,肺阻力也无显著变化。然而,本研究获得的数据表明,口服异波帕明能够产生静脉注射多巴胺在麻醉犬身上所诱导的大部分效应。异波帕明对心脏和肾脏的作用可能为人类慢性心力衰竭的长期治疗开辟新的前景。

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