The adrenocorticotropic hormone (ACTH)-induced reversal of hemorrhagic shock.

Abstract

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.

• Authors: A Bertolini, W Ferrari, S Guarini
• Journal: Resuscitation (Resuscitation) Vol. 18 Issue 2-3 Pg. 253-67 (Dec 1989) ISSN: 0300-9572 [Print] Ireland
• PMID: 2555878 (Publication Type: Journal Article)

Chemical References

• Adrenocorticotropic Hormone

Topics

• Adrenocorticotropic Hormone (analogs & derivatives, therapeutic use)
• Animals
• Dose-Response Relationship, Drug
• Hemodynamics (drug effects)
• Rats
• Shock, Hemorrhagic (drug therapy)