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长时间热损伤后交感神经和肾上腺髓质耗竭中多巴胺(3-羟酪胺)的替代与代谢

Dopamine (3-hydroxytyramine) replacement and metabolism in sympathetic nerve and adrenal medullary depletions after prolonged thermal injury.

作者信息

Goodall M C, Alton H

出版信息

J Clin Invest. 1969 Sep;48(9):1761-7. doi: 10.1172/JCI106142.

DOI:10.1172/JCI106142
PMID:5822584
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC535748/
Abstract

After severe thermal injury, the adrenal medulla and the sympathetic nerves can be partially or totally depleted of their adrenaline (epinephrine) and noradrenaline (norepinephrine). The purpose of this paper is to elucidate the rate at which dopamine-2-(14)C, a precursor of noradrenaline, is synthesized into noradrenaline and noradrenaline metabolic products, thereby giving some indication as to dopamine's utilization, turnover, and possible use in treating such noradrenaline-adrenaline depletions. Three burned subjects, 3 wk postburn, were infused with 104.6 muc (872 mug) of dopamine-2-(14)C for 4 hr. Urine was collected at various hourly intervals for the 1st day, and thereafter for 4 days, assayed, and compared with the metabolism of dopamine in normal subjects. Methods for separating, identifying, and counting radioactivity of the various metabolic products of dopamine are described. Normally 87.6 +/-3.1% of the total radioactivity is recovered within 24 hr after an infusion of dopamine-2-(14)C, but in the three severely burned patients, this value was increased to 93.1, 97.3, and 97.5% in 24 hr. There was a marked decrease in the percentage of radioactivity recovered as noradrenaline in all collection periods, and in contrast to normal subjects, no radioactive noradrenaline was recovered after 24 hr. Concomitantly, there was an increase in radioactivity recovered as metabolic products of noradrenaline, reflecting a compensatory shift toward noradrenaline synthesis and utilization at the expense of the dopamine metabolic products. The results indicate that in the burned patients the infused dopamine-2-(14)C was rapidly synthesized into noradrenaline and then rapidly released and metabolized. From these results it seems evident that dopamine would be a useful adjunct in the treatment of sympathico-adrenal medullary depletion in burns.

摘要

严重热损伤后,肾上腺髓质和交感神经中的肾上腺素(epinephrine)和去甲肾上腺素(norepinephrine)可能会部分或全部耗尽。本文的目的是阐明去甲肾上腺素的前体多巴胺 - 2 -(14)C合成去甲肾上腺素及其代谢产物的速率,从而对多巴胺的利用、周转情况以及在治疗此类去甲肾上腺素 - 肾上腺素耗竭方面的可能用途提供一些线索。三名烧伤患者在烧伤后3周,静脉输注104.6微居里(872微克)的多巴胺 - 2 -(14)C,持续4小时。在第1天的不同时间间隔每小时收集尿液,此后4天也进行收集、检测,并与正常受试者的多巴胺代谢情况进行比较。文中描述了分离、鉴定和计数多巴胺各种代谢产物放射性的方法。正常情况下,输注多巴胺 - 2 -(14)C后24小时内,总放射性的87.6±3.1%可被回收,但在这三名严重烧伤患者中,该值在24小时内分别增至93.1%、97.3%和97.5%。在所有收集时间段内,以去甲肾上腺素形式回收的放射性百分比显著降低,与正常受试者不同的是,24小时后未回收放射性去甲肾上腺素。与此同时,作为去甲肾上腺素代谢产物回收的放射性增加,这反映了以多巴胺代谢产物为代价,向去甲肾上腺素合成和利用的代偿性转变。结果表明,在烧伤患者中,输注的多巴胺 - 2 -(14)C迅速合成去甲肾上腺素,然后迅速释放并代谢。从这些结果来看,多巴胺似乎是治疗烧伤中交感 - 肾上腺髓质耗竭的一种有用辅助药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c08/535748/6ff8de4cb09e/jcinvest00215-0194-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c08/535748/bc1e2bdecba9/jcinvest00215-0191-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c08/535748/6ff8de4cb09e/jcinvest00215-0194-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c08/535748/bc1e2bdecba9/jcinvest00215-0191-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c08/535748/6ff8de4cb09e/jcinvest00215-0194-a.jpg

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本文引用的文献

1
Sympathetic Nerve Depletion in Severe Thermal Injury.严重热损伤中的交感神经耗竭
Ann Surg. 1965 Nov;162(5):893-900. doi: 10.1097/00000658-196511000-00013.
2
Catecholamine excretion and personality traits in paratroop trainees.伞兵学员的儿茶酚胺排泄与人格特质
Acta Physiol Scand. 1963 May;58:77-89. doi: 10.1111/j.1748-1716.1963.tb02630.x.
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Sympathoadrenal response to gravitational stress.交感肾上腺对重力应激的反应。
Clin Pharmacokinet. 1994 Nov;27(5):345-67. doi: 10.2165/00003088-199427050-00003.
4
Dopamine (3-hydroxytyramine) metabolism in parkinsonism.帕金森病中的多巴胺(3-羟酪胺)代谢
J Clin Invest. 1969 Dec;48(12):2300-8. doi: 10.1172/JCI106196.
5
Decreased noradrenaline (norepinephrine) synthesis in familial dysautonomia.家族性自主神经功能异常中去甲肾上腺素合成减少。
J Clin Invest. 1971 Dec;50(12):2734-40. doi: 10.1172/JCI106774.
6
The separation of epinephrine from norepinephrine and dopamine from DOPA on Sephadex G-10.在葡聚糖凝胶G - 10上对肾上腺素与去甲肾上腺素以及多巴与多巴胺进行分离。
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Catecholamines: mediator of the hypermetabolic response to thermal injury.儿茶酚胺:热损伤后高代谢反应的介质。
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8
Role of O-methylation in the renal excretion of catecholamines in dogs.O-甲基化在犬类儿茶酚胺肾排泄中的作用。
Naunyn Schmiedebergs Arch Pharmacol. 1973;277(4):373-86. doi: 10.1007/BF00500997.
J Clin Invest. 1962 Feb;41(2):197-202. doi: 10.1172/JCI104471.
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Adrenal medullary insufficiency in severe thermal burn.严重热烧伤中的肾上腺髓质功能不全
J Clin Invest. 1960 Dec;39(12):1927-32. doi: 10.1172/JCI104217.
5
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Ann Surg. 1957 Apr;145(4):479-87. doi: 10.1097/00000658-195704000-00004.
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J Clin Endocrinol Metab. 1954 Jun;14(6):608-21. doi: 10.1210/jcem-14-6-608.
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