Greig Lynn D, Leslie Stephen J, Gibb Fraser W, Tan Sherilyn, Newby David E, Webb David J
Western General Hospital, Edinburgh, UK.
Br J Clin Pharmacol. 2005 Mar;59(3):265-70. doi: 10.1111/j.1365-2125.2004.02334.x.
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.
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.
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.
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.
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。
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。
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。
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。