ACTH Infusion Impairs Baroreflex Sensitivity-Implications for Cardiovascular Hypoglycemia-Associated Autonomic Failure.
ACTH
autonomic failure
baroreflex
cortisol
hypoglycemia
Journal
The Journal of clinical endocrinology and metabolism
ISSN: 1945-7197
Titre abrégé: J Clin Endocrinol Metab
Pays: United States
ID NLM: 0375362
Informations de publication
Date de publication:
01 07 2020
01 07 2020
Historique:
received:
05
02
2020
accepted:
27
04
2020
pubmed:
1
5
2020
medline:
4
2
2021
entrez:
1
5
2020
Statut:
ppublish
Résumé
Hypoglycemia attenuates cardiovascular homeostatic autonomic control. This attenuation, known as the cardiovascular component of hypoglycemia-associated autonomic failure (HAAF), is characterized most notably by decreased baroreflex sensitivity (BRS) that begins during hypoglycemia and persists until at least the next day, despite return to euglycemia. Understanding the mechanisms underlying this reduction in BRS is important because BRS attenuation is associated with increased morbidity and mortality. The objective of this work is to investigate the role of the adrenocorticotropin (ACTH)-adrenal axis in decreasing BRS. We tested the hypothesis that infusion of ACTH 1-24 (cosyntropin), as compared to placebo, would acutely suppress BRS, and that this decrease in BRS would be present the next day. A double-blind, placebo-controlled, random-order, cross-over study was conducted. This study took place in a clinical research center. Participants included healthy men and women. Interventions included an intravenous infusion of cosyntropin (70 μg/hour for 2.5 hours in the morning and again in the early afternoon) vs normal saline placebo. Outcome measures included BRS during and 16 hours after cosyntropin vs placebo infusions. Cosyntropin infusion attenuated BRS (mm Hg/ms) as compared to placebo (baseline 17.8 ± 1.38 vs 17.0 ± 2.07; during 14.4 ± 1.43 vs 17.3 ± 1.65; and next day 14.8 ± 1.42 vs 18.9 ± 2.04; P < .05, time by treatment, analysis of variance). BRS was decreased during the final 30 minutes of the morning cosyntropin infusion as compared to baseline (P < .01) and remained suppressed the next day (16 hours after afternoon infusion) (P < .025). Placebo infusion did not significantly change BRS. Corrected QT interval was not affected. ACTH attenuates BRS, raising the possibility that hypoglycemia-induced increases in ACTH may contribute to the cardiovascular component of HAAF.
Identifiants
pubmed: 32353115
pii: 5827417
doi: 10.1210/clinem/dgaa221
pmc: PMC7255850
pii:
doi:
Substances chimiques
Cosyntropin
16960-16-0
Banques de données
ClinicalTrials.gov
['NCT02339506']
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NHLBI NIH HHS
ID : K24 HL103845
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL007609
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001102
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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