We continue our discussion of renal ischemia with the early history of one of the most common proposed therapies to address this problem.
What is "renal dose dopamine" and how was it discovered?
我们继续讨论接受常规治疗的病人出现早期肾脏缺血的情况：
何谓肾脏剂量多巴胺？其是如何被发现的？
参考答案：
肾脏剂量多巴胺指多巴胺的低速输注，因为认为该剂量DA可增加肾血流速度而常用于临床。相对于去甲肾上腺素，DA是一儿茶酚胺类物质前体，其肾脏效应是Dr. Leon Goldberg发现的，他在20世纪60年代中发表了一系列关于DA所特有而其他儿茶酚胺类物质所不具有的特点的文章。第一篇文章发表早1963年[1]，是关于4例有严重CHF患者使用DA治疗的报道，治疗目的是利用DA的变时性和变力性以产生利尿作用。Goldberg发现的肾小球滤过率（GFR）、尿量和钠排出量均增加，但是钠排出量和尿量的程度远远超过了使用其他儿茶酚胺类物质时。
此后对9名健康志愿者和6名CHF患者进行了研究[2]。每例对象接受不增加心率或血压的最大剂量的DA输注。不同对象间的输注速度范围为2.6~7.1 mcg/kg/min。健康志愿者中GFR、估计肾血浆流量（ERPF）、尿量和钠排量增加。而CHF病人则只有钠排量显著增加。需要注意的是，6名CHF中的2例出现心绞痛症状，1例在使用DA期间室性期前收缩增加而必须停止使用DA。
接着，Goldberg使用犬模型对该发现进行直接研究[3]。其显露每条犬的肾动脉，并放置一流量探测器于股动脉和肾动脉周围。其对全身输注DA和直接输注DA到动脉进行了效果观察。结果发现，全身输注时通过股动脉的血流减少而肾动脉血流增加。这种现象也同样在直接动脉输注DA组中存在，即使肾动脉血流在使用较高剂量DA情况下开始减少。肾血流产生最大持续增加的输注速度为1.2 mcg/kg/min，这与现在使用的剂量非常接近。建立在这些发现基础上，Goldberg断定必然存在一个独立的DA受体，并预言：DA具有改变心输出量分布从而益于肾脏的能力将发挥有效的临床作用。
What is "renal dose dopamine" and how was it discovered?
The term "renal dose dopamine" refers to a low-rate dopamine infusion, and it is in common clinical use because it is believed to increase blood flow to the kidney. Dopamine is a catecholamine precursor to norepinephrine, and the discovery of its renal effects can be attributed to Dr. Leon Goldberg, who published a series of papers in the mid-1960's describing unique properties to dopamine which were not found in other catecholamines. The first paper appeared in 1963 (1), and was a case series of four patients with severe CHF who were treated with dopamine; the goal was to take advantage of dopamine's chronotropic and inotropic properties to induce a diuresis. Goldberg found that glomerular filtration rate (GFR), urine output and sodium excretion all increased, but the degree of sodium excretion and urine output far exceeded what had been observed with other catecholamines.
This paper was followed by a study of nine healthy volunteers and six patients with CHF (2). Each subject was treated with an infusion of dopamine at the highest rate which did not increase heart rate or blood pressure. This rate varied from 2.6 mcg/kg/min to 7.1 mcg/kg/min amongst the different subjects. The healthy volunteers showed increases in GFR, estimated renal plasma flow (ERPF), urine output and sodium excretion. The patients with CHF however, showed a significant increase only in sodium excretion. Of note, two of the six patients with CHF developed anginal symptoms and one an increased number of ventricular premature beats during dopamine treatment, necessitating cessation of the infusion.
Next, Goldberg used a dog model to study this finding more directly (3). He exposed a renal artery on each dog and placed a flow probe around both the femoral artery and renal artery. He then observed the effects of dopamine when infused systemically and by direct injection into the arteries. He found with systemic injection that flow decreaed through the femoral artery and increased through the renal artery. This was also seen when dopamine was injected directly, although the renal artery began to exhibit decreased flows at higher levels of dopamine injection. The infusion rate which produced the largest consistent increase in renal blood flow was 1.2 mcg/kg/min, very close to what is used today. On the basis of these findings, Goldberg posited the existence of a separate receptor for dopamine, and predicted that dopamine's ability to alter the distribution of cardiac output in favor of the kidney would "find useful clinical applications."
References:
1.Goldberg, L. et al. Sodium diuresis produced by dopamine in patients with congestive heart failure. New Engl J Med 1963; 269(20): 1060-4.
2.Golberg, L. et al. Effects of dopamine in man: augmentation of sodium excretion, glomerular filtration rate, and renal plasma flow. J Clin Invest 1964; 43:1116-24.
3.Goldberg, L. et al. Direct renal vasodilatation produced by dopamine in the dog. Circ Res 1965; 16: 510-7.
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