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硝酸甘油和亚硝酸异戊酯对脉搏波反射及增强指数的比较效应。

Comparative effects of glyceryl trinitrate and amyl nitrite on pulse wave reflection and augmentation index.

作者信息

Greig Lynn D, Leslie Stephen J, Gibb Fraser W, Tan Sherilyn, Newby David E, Webb David J

机构信息

Western General Hospital, Edinburgh, UK.

出版信息

Br J Clin Pharmacol. 2005 Mar;59(3):265-70. doi: 10.1111/j.1365-2125.2004.02334.x.

Abstract

AIMS

The influence of vasodilators on augmentation index (AIx) offers a simple, rapid and noninvasive method of evaluating vascular function. Glyceryl trinitrate (GTN) is widely used as an endothelium-independent vasodilator, although other nitrates that are shorter acting may have advantages in clinical studies. The aim of this study was to compare the effects of two short-acting nitrates, GTN and amyl nitrite, which have differing pharmacodynamic profiles.

METHODS

Twenty-one healthy volunteers (15 male; mean age 35 years, range 21-56 years) attended on three occasions and received sublingual GTN (0.5 mg for 3 min), inhaled amyl nitrite (0.2 ml inhaled for 30 s), or no treatment in a randomized cross-over design. Haemodynamic responses of AIx, blood pressure and thoracic bioimpedance (heart rate, cardiac index) were assessed by measurement at baseline, every 60 s for the first 5 min, and then every 5 min for a further 55 min.

RESULTS

AIx was reduced by amyl nitrite (peak effect -9 +/- 2% at 1 min, P < 0.002) and GTN (peak effect -12 +/- 3% at 4 min, P < 0.05). Compared with amyl nitrite, the onset and offset of action of GTN was slower. Amyl nitrite initially increased heart rate by 27 +/- 4% (P < 0.001) and cardiac index by 13 +/- 3% (P < 0.001) whereas GTN had no significant effect (P > 0.05). Neither agent affected blood pressure.

CONCLUSIONS

GTN causes a slower and more sustained reduction in AIx than amyl nitrite. Although amyl nitrite causes a more rapid fall and recovery in AIx, it induces a reflex tachycardia that may limit interpretation of the initial (1 min) but not later (2 min) changes in AIx. The prolonged offset of GTN suggests that a sufficient washout period must be included when making repeated measures or when assessing the subsequent effects of other agents.

摘要

目的

血管扩张剂对增强指数(AIx)的影响提供了一种评估血管功能的简单、快速且无创的方法。硝酸甘油(GTN)作为一种不依赖内皮的血管扩张剂被广泛使用,尽管其他作用时间较短的硝酸盐在临床研究中可能具有优势。本研究的目的是比较两种具有不同药效学特征的短效硝酸盐,即GTN和亚硝酸异戊酯的效果。

方法

21名健康志愿者(15名男性;平均年龄35岁,范围21 - 56岁)分三次参加研究,采用随机交叉设计,分别接受舌下含服GTN(0.5毫克,持续3分钟)、吸入亚硝酸异戊酯(0.2毫升,吸入30秒)或不接受治疗。通过在基线时测量以及在最初5分钟内每60秒测量一次,随后在另外55分钟内每5分钟测量一次,来评估AIx、血压和胸部生物阻抗(心率、心脏指数)的血流动力学反应。

结果

亚硝酸异戊酯使AIx降低(1分钟时峰值效应为 -9±2%,P < 0.002),GTN也使AIx降低(4分钟时峰值效应为 -12±3%,P < 0.05)。与亚硝酸异戊酯相比,GTN的起效和作用消失较慢。亚硝酸异戊酯最初使心率增加27±4%(P < 0.001),使心脏指数增加13±3%(P < 0.001),而GTN无显著影响(P > 0.05)。两种药物均不影响血压。

结论

与亚硝酸异戊酯相比,GTN使AIx降低的速度更慢且更持久。尽管亚硝酸异戊酯使AIx下降和恢复更快,但它会诱发反射性心动过速,这可能会限制对AIx初始(1分钟)而非后续(2分钟)变化的解读。GTN作用消失时间延长表明,在进行重复测量或评估其他药物的后续效应时,必须包含足够的洗脱期。

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