吗啡诱发的通气抑制中的性别差异存在于外周化学反射环内。

Sex differences in morphine-induced ventilatory depression reside within the peripheral chemoreflex loop.

作者信息

Sarton E, Teppema L, Dahan A

机构信息

Department of Anesthesiology, Leiden University Medical Center, The Netherlands.

出版信息

Anesthesiology. 1999 May;90(5):1329-38. doi: 10.1097/00000542-199905000-00017.

DOI:10.1097/00000542-199905000-00017

PMID:10319781

Abstract

BACKGROUND

This study gathers information in humans on the sites of sex-related differences in ventilatory depression caused by the mu-opioid receptor agonist morphine.

METHODS

Experiments were performed in healthy young men (n = 9) and women (n = 7). Dynamic ventilatory responses to square-wave changes in end-tidal carbon dioxide tension (7.5-15 mmHg) and step decreases in end-tidal oxygen tension (step from 110 to 50 mmHg, duration of hypoxia 15 min) were obtained before and during morphine infusion (intravenous bolus dose 100 microg/kg, followed by 30 microg x kg(-1) x h(-1)). Each hypercapnic response was separated into a fast peripheral and slow central component, which yield central (Gc) and peripheral (Gp) carbon dioxide sensitivities. Values are mean +/- SD.

RESULTS

In carbon dioxide studies in men, morphine reduced Gc from 1.61 +/- 0.33 to 1.23 +/- 0.12 l x min(-1) x mmHg(-1) (P < 0.05) without affecting Gp (control, 0.41 +/- 0.16 and morphine, 0.49 +/- 0.12 l x min(-1) x mmHg(-1), not significant). In carbon dioxide studies in women, morphine reduced Gc, from 1.51 +/- 0.74 to 1.17 +/- 0.52 l x min(-1) x mmHg(-1) (P < 0.05), and Gp, from 0.54 +/- 0.19 to 0.39 +/- 0.22 l x min(-1) x mmHg(-1) (P < 0.05). Morphine-induced changes in Gc were equal in men and women; changes in Gp were greater in women. In hypoxic studies, morphine depressed the hyperventilatory response at the initiation of hypoxia more in women than in men (0.54 +/- 0.23 vs. 0.26 +/- 0.34 l x min(-1) x %(-1), respectively; P < 0.05). The ventilatory response to sustained hypoxia (i/e., 15 min) did not differ between men and women.

CONCLUSIONS

The data indicate the existence of sex differences in morphine-induced depression of responses mediated via the peripheral chemoreflex pathway, with more depression in women, but not of responses mediated via the central chemoreflex pathway. In men and women, morphine did not change the translation of the initial hyperventilatory response to short-term hypoxia into the secondary decrease in inspired minute ventilation (Vi) caused by sustained hypoxia.

摘要

背景

本研究收集人体中由μ阿片受体激动剂吗啡引起的通气抑制中性别相关差异的部位信息。

方法

在健康年轻男性（n = 9）和女性（n = 7）中进行实验。在输注吗啡前和期间（静脉推注剂量100μg/kg，随后以30μg·kg⁻¹·h⁻¹持续输注），获取对潮气末二氧化碳分压方波变化（7.5 - 15 mmHg）和潮气末氧分压阶跃下降（从110降至50 mmHg，低氧持续时间15分钟）的动态通气反应。每个高碳酸血症反应被分为快速外周和缓慢中枢成分，从而得出中枢（Gc）和外周（Gp）二氧化碳敏感性。数值为平均值±标准差。

结果

在男性的二氧化碳研究中，吗啡使Gc从1.61±0.33降至1.23±0.12 l·min⁻¹·mmHg⁻¹（P < 0.05），而不影响Gp（对照组为0.41±0.16，吗啡组为0.49±0.12 l·min⁻¹·mmHg⁻¹，无显著差异）。在女性的二氧化碳研究中，吗啡使Gc从1.51±0.74降至1.17±0.52 l·min⁻¹·mmHg⁻¹（P < 0.05），使Gp从0.54±0.19降至0.39±0.22 l·min⁻¹·mmHg⁻¹（P < 0.05）。吗啡引起的Gc变化在男性和女性中相同；Gp的变化在女性中更大。在低氧研究中，吗啡在低氧开始时对女性通气反应的抑制作用比对男性更大（分别为0.54±0.23与0.26±0.34 l·min⁻¹·%⁻¹；P <