Bertolini A, Ferrari W, Guarini S
Institute of Pharmacology, University of Modena, Italy.
Resuscitation. 1989 Dec;18(2-3):253-67. doi: 10.1016/0300-9572(89)90027-0.
Adrenocorticotropic hormone (ACTH), while having negligible effects on cardiovascular function in the intact animal, induces a potent and sustained reversal of an otherwise invariably, rapidly fatal condition of hemorrhage-induced hypovolemic shock, in rats and dogs. The main site(s) of action are at the peripheral level; however, subsidiary site(s) of action in the CNS cannot be excluded. The studies on the mechanism of action indicate that the ACTH-induced reversal of hemorrhagic shock (a) is an extra-hormonal, adrenal-independent effect, because it is not affected by adrenalectomy and is shared by many ACTH-fragments practically devoid of corticotropic activity; (b) is antagonized by morphine in a surmontable way; (c) needs the functional integrity of the sympathetic nervous system (it is prevented by guanethidine, reserpine, and clonidine) and the availability of peripheral alpha-adrenoceptors (it is antagonized by dibenamine, prazosin and yohimbine, but not by practolol); (d) requires the integrity of afferent vagal fibers (it is almost completely abolished by vagotomy); (e) involves central cholinergic networks (it is antagonized by atropine sulphate, but not by atropine methyl bromide; and it is prevented by the intracerebroventricular injection of hemicholinium-3); (f) is associated with a massive increase in the volume of circulating blood, likely due to a mobilization from peripheral pooling sites (it is largely prevented by splenectomy or by suprahepatic veins ligature, and is associated with a restoration of the venous blood flow in peripheral vascular beds and with a normalization of venous PO2); (g) is associated with a restoration of heart and spleen adrenoceptors, whose number is significantly decreased during hemorrhagic shock. The survival time of hemorrhage-shocked animals, which is 26 +/- 3 min in controls, is greatly prolonged (44 +/- 18 h) by ACTH, provided that the treatment is made within 5-10 min after bleeding. Finally, in animals treated with ACTH within 5-10 min after bleeding, blood reinfusion retains its effectiveness and reverse shock even if performed 2-5 h later.
促肾上腺皮质激素（ACTH）对完整动物的心血管功能影响可忽略不计，但在大鼠和狗身上，它能有效且持续地逆转因出血性低血容量性休克导致的一种通常迅速致命的状况。其主要作用部位在外周水平；然而，不能排除中枢神经系统中的次要作用部位。关于作用机制的研究表明，ACTH诱导的出血性休克逆转（a）是一种非激素、不依赖肾上腺的效应，因为它不受肾上腺切除术的影响，且许多几乎没有促肾上腺皮质活性的ACTH片段也有此作用；（b）可被吗啡以可克服的方式拮抗；（c）需要交感神经系统的功能完整性（可被胍乙啶、利血平和可乐定阻断）以及外周α - 肾上腺素能受体的可用性（可被酚苄明、哌唑嗪和育亨宾拮抗，但不被心得宁拮抗）；（d）需要传入迷走神经纤维的完整性（迷走神经切断术几乎可完全消除此作用）；（e）涉及中枢胆碱能网络（可被硫酸阿托品拮抗，但不被甲基溴化阿托品拮抗；脑室内注射半胱氨酸3可阻断此作用）；（f）与循环血量的大量增加有关，这可能是由于外周血液池部位的动员（脾切除术或肝上静脉结扎术可在很大程度上阻断此作用，且与外周血管床静脉血流的恢复以及静脉血氧分压的正常化有关）；（g）与心脏和脾脏肾上腺素能受体的恢复有关，在出血性休克期间其数量会显著减少。出血性休克动物的存活时间在对照组中为26±3分钟，若在出血后5 - 10分钟内给予ACTH治疗，则存活时间会大幅延长（44±18小时）。最后，在出血后5 - 10分钟内接受ACTH治疗的动物，即使在2 - 5小时后进行输血，输血仍能有效逆转休克。
