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[每周一问]NO.18-Alpha 2 Adrenoceptor Agonists

1.  What are the cardiovascular effects of alpha 2 agonists?
2.  Can the cardiovascular responses to alpha 2 agonists be reversed or treated?
1.  α-2受体激动剂的心血管效应是什么？
2.  α-2受体激动剂的心血管反应能否被逆转或治疗？如果能，如何逆转或治疗？

参考答案
1.α-2受体激动剂的心血管效应是什么？
通过其对交感神经系统的作用，α-2肾上腺素受体激动剂降低阻力血管和容量血管的张力、心肌收缩力、心率[1]。然而，在离体心脏标本中发现，这些激动剂的抑制效果是非直接的[2]。总的来说，其导致心输出量和全身外周血管阻力的降低，合并有全身血容量的重新分布。Talke等[1]在对绵羊的长期控制研究发现，给与产生镇静作用的美托咪定（α-2肾上腺素受体激动剂）剂量，血流动力学数值和器官血流（使用染色微球法）减小，此外，他们还发现，虽然阿替美唑（α-2受体激动剂）翻转美托咪定的血流动力学和镇静效果，但是却不能完全翻转优先重新分布大脑、心脏和肾脏的血流到骨骼肌血流方式。他们得出结论认为，α-2受体激动剂的反转效应比传统激动剂/拮抗剂相互关系更复杂。
对血压的作用，α-2受体激动剂的作用是双向的，在小剂量和大剂量下分别为降低和增加全身压力[3]。该作用被假设发生，通过对来自于中枢神经系统的交感系统的最初抑制，伴有相关的血管阻力的降低，并伴随着外周血管受体介导的血管收缩的增加[1，4]。
给与α-2受体激动剂后较少出现的作用包括心动过缓和窦房性传导阻滞，这些作用更常发生在年轻人，因为其副交感神经张力处于高水平[5]。

2.α-2受体激动剂的心血管反应能否被逆转或治疗？
心动过缓可以通过阿托品治疗，虽然有时候需要大剂量[6]。麻黄素和苯肾上腺素可治疗低血压，然而可以观察到存在过度缩血管反应，因为α-2受体激动剂导致压力感受器反射[7]和α-1肾上腺素受体介导的血管收缩作用增强[8]。在这两个研究中[7，8]，麻黄素和苯肾上腺素在使用α-2受体激动剂（可乐定）后的升压效果增强在清醒和麻醉（安氟醚和笑气）病人没有差别。

What are the cardiovascular effects of alpha 2 agonists?
Through their actions on the sympathetic nervous system, alpha 2 agonists decrease the tone of resistance and capacitance vessels, myocardial contractility, and heart rate (1). No direct depressant effect of these agents, however, has been demonstrated in isolated heart preparations (2). Overall, these effects lead to a decrease in cardiac output and total peripheral resistance, combined with a redistribution in systemic blood flow. Talke et al.(1) noted in chronically instrumented sheep, that hemodynamic values and organ blood flow (using colored microspheres) decreased with doses of medetomidine (alpha 2 agonist) necessary to produce sedation. Moreover, they noted that although atipamezole (alpha 2 antagonist) reversed the hemodynamic and sedative effects of medetomidine, it failed to completely reverse the blood flow pattern, which was preferentially redistributed from the brain, heart, and kidney to the skeletal muscle. The authors concluded that the reversal of alpha 2 agonist effects may be more complex than a traditional agonist/antagonist interaction.
In terms of their effect on blood pressure, alpha 2 agonists have a biphasic effect, decreasing and increasing systemic pressures at small and large doses, respectively (3). This effect has been hypothesized to occur through an initial reduction in sympathetic outflow from the central nervous system with its associated decrease in vascular resistance, followed by a peripheral vascular receptor mediated increase in vasoconstriction (1,4).
Other less frequent occurrences with administration of alpha 2 agonists include bradycardia and sinoauricular block, which have been suggested to occur more commonly in young patients due to their high level of parasympathetic tone (5).
Can the cardiovascular responses to alpha 2 agonists be reversed or treated?
Bradycardia can be treated with atropine, although high doses are sometimes necessary . Ephedrine and phenylephrine can treat the hypotension, however an amplified vasoconstrictive response may be observed due to an alpha 2 agonist induced enhancement of baroreceptor reflexes (7) and potentiation of alpha 1-adrenoceptor-mediated vasoconstriction . In these two studies by the same Japanese group (7, 8), the enhanced pressor effects of ephedrine and phenylephrine following an alpha 2 agonist (clonidine) were no different between awake and anesthetized (enflurane and nitrous oxide in oxygen) patients.
References:
1.  Talke PO, Traber DL, Richardson CA et al. The effect of alpha (2) agonist-induced sedation and its reversal with an alpha (2) antagonist on organ blood flow in sheep. Anesth Analg 2000;90(5):1060-6.
2.  Flacke WE, Flacke JW, Blow KD, et al. Effect of dexmedetomidine, an alpha 2 adrenergic agonist, in the isolated heart. J Cardiothorac Vasc Anesth 1992;6:418-23.
3.  Savola JM. Cardiovascular actions of medetomidine and their reversal by atipamezole. Acta Vet Scand 1989;85:39-47.
4.  Flacke JW, Flacke WE. Clonidine prevention of myocardial ischemia during cardiac surgery: will this change outcome? (editorial) J Cardiothorac Vasc Anesth 1993;7:383-5.
5.  DeBels D, Coriat P. Alpha 2 adrenoceptor agonists: An increasing role in modern anesthesia. Problems in Anesthesia 2000;12:65-72.
6.  Nishikawa T, Dohi S. Oral clonidine blunts the heart rate response to intravenous atropine in humans. Anesthesiology 1991:75:217-22.
7.  Nishikawa T, Kimura T, Taguchi N, et al. Oral clonidine preanesthetic medication augments the pressor responses to intravenous ephedrine in awake or anesthetized patients. Anesthesiology 1991;74:705-10.
8.  Inomata S, Nishikawa T, Kihara S, Akiyoshi Y. Enhancement of pressor response to intravenous phenylephrine following oral clonidine medication in awake and anaesthetized patients. Can J Anaesth 1995 Feb;42(2):119-25.
Site Editor: Stephen B. Corn, M.D. and B. Scott Segal, M.D.
Department of Anesthesia, Harvard Medical School
Founders and Editors-in-Chief: Stephen B. Corn, M.D. and B. Scott Segal, M.D.
Department of Anesthesiology, Perioperative and Pain Medicine, Harvard Medical School