ACTH 输注损害压力感受反射敏感性-对心血管低血糖相关自主神经衰竭的影响。

ACTH Infusion Impairs Baroreflex Sensitivity-Implications for Cardiovascular Hypoglycemia-Associated Autonomic Failure.

机构信息

Division of Endocrinology and Diabetes, Virginia Mason Medical Center, Seattle, Washington.

Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.

出版信息

J Clin Endocrinol Metab. 2020 Jul 1;105(7):2345-53. doi: 10.1210/clinem/dgaa221.

DOI:10.1210/clinem/dgaa221

PMID:32353115

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7255850/

Abstract

CONTEXT

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.

OBJECTIVE

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.

DESIGN

A double-blind, placebo-controlled, random-order, cross-over study was conducted.

SETTING

This study took place in a clinical research center.

PARTICIPANTS

Participants included healthy men and women.

INTERVENTIONS

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.

MAIN OUTCOME MEASURES

Outcome measures included BRS during and 16 hours after cosyntropin vs placebo infusions.

RESULTS

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.

CONCLUSIONS

ACTH attenuates BRS, raising the possibility that hypoglycemia-induced increases in ACTH may contribute to the cardiovascular component of HAAF.

摘要

背景

低血糖会减弱心血管自主神经稳态控制。这种减弱被称为低血糖相关自主神经衰竭（HAAF）的心血管成分，其特征主要是压力反射敏感性（BRS）降低，这种降低始于低血糖期间，并持续到至少第二天，尽管血糖已恢复正常。了解这种 BRS 降低的机制很重要，因为 BRS 减弱与发病率和死亡率增加有关。

目的

本研究旨在探讨促肾上腺皮质激素（ACTH）-肾上腺轴在降低 BRS 中的作用。我们假设与安慰剂相比，ACTH 1-24（合成促皮质素）输注会急性抑制 BRS，并且这种 BRS 降低会在第二天出现。

设计

这是一项双盲、安慰剂对照、随机交叉研究。

地点

该研究在临床研究中心进行。

参与者

参与者包括健康的男性和女性。

干预措施

干预措施包括静脉输注合成促皮质素（上午 70μg/h，持续 2.5 小时，下午再输注一次）与生理盐水安慰剂。

主要观察指标

观察指标包括合成促皮质素与安慰剂输注期间和输注后 16 小时的 BRS。

结果

与安慰剂相比，合成促皮质素输注减弱了 BRS（mmHg/ms）（基础值 17.8±1.38 比 17.0±2.07；期间 14.4±1.43 比 17.3±1.65；第二天 14.8±1.42 比 18.9±2.04；P<0.05，方差分析）。与基线相比，上午合成促皮质素输注的最后 30 分钟内 BRS 降低（P<0.01），第二天（下午输注后 16 小时）仍受抑制（P<0.025）。安慰剂输注并未显著改变 BRS。校正后的 QT 间期不受影响。