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大肠杆菌内毒素诱导的休克期间多巴酚丁胺与一种新型多巴胺衍生物(D4975)心血管效应的比较。

A comparison of the cardiovascular effects of dobutamine and a new dopamine derivative (D4975) during shock induced by E. coli endotoxin.

作者信息

McCaig D, Parratt J R

出版信息

Br J Pharmacol. 1980 Aug;69(4):651-6. doi: 10.1111/j.1476-5381.1980.tb07917.x.

Abstract

1 The effects of a newly developed dopamine-xanthine derivative, 7-propyl-theophylline-dopamine (D4975) and of dobutamine have been examined in anaesthetized cats before and after the induction of shock with E. coli endotoxin. 2 Both D4975 and dobutamine caused dose-related increases in left ventricular (LV) dP/dtmax (and LVdP/dt at fixed isovolumic pressures. Significantly smaller increases in LVdP/dtmax occurred as early as 0.5 to 1 h after endotoxin, with maximal attenuation at 1 to 2 h and some improvement in sensitivity in cats surviving 2 to 4 h. The maximum response to each drug was markedly reduced in shock. 3 Neither D4975 nor dobutamine had significant effects on heart rate. D4975 caused dose-related increases in systemic arterial blood pressure which were smaller during shock, the changes in responsiveness following those in LVdP/dtmax. 4 Possible mechanisms responsible for changing myocardial sensitivity to these and other agents are discussed. It is concluded that D4975 may be more useful in the treatment of shock than either dopamine or dobutamine because (a) it is more potent during shock than dobutamine (perhaps as a result of phosphodiesterase inhibition by the theophylline component of D4975); (b) its action is longer-lasting than dobutamine or dopamine and (c) like dobutamine, its effect on heart rate is insignificant.

摘要
  1. 研究了一种新开发的多巴胺 - 黄嘌呤衍生物7 - 丙基 - 茶碱 - 多巴胺(D4975)和多巴酚丁胺在大肠杆菌内毒素诱导休克前后对麻醉猫的作用。2. D4975和多巴酚丁胺均引起左心室(LV)dP/dtmax(以及在固定等容压力下的LVdP/dt)呈剂量相关的增加。内毒素注射后最早在0.5至1小时,LVdP/dtmax的增加明显变小,在1至2小时时达到最大减弱程度,而在存活2至4小时的猫中敏感性有所改善。在休克状态下,每种药物的最大反应均明显降低。3. D4975和多巴酚丁胺对心率均无显著影响。D4975引起全身动脉血压呈剂量相关的增加,在休克期间这种增加较小,其反应性变化跟随LVdP/dtmax的变化。4. 讨论了导致心肌对这些及其他药物敏感性改变的可能机制。得出的结论是,D4975在休克治疗中可能比多巴胺或多巴酚丁胺更有用,因为(a)在休克期间它比多巴酚丁胺更有效(可能是由于D4975的茶碱成分抑制磷酸二酯酶);(b)其作用比多巴酚丁胺或多巴胺更持久;(c)与多巴酚丁胺一样,它对心率的影响不显著。

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Pathophysiology of endotoxin shock in the primate.灵长类动物内毒素休克的病理生理学
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