Hayward Christopher S, Kraidly Mustafa, Webb Carolyn M, Collins Peter
Cardiology Department, St. Vincent's Hospital, Sydney, New South Wales, Australia.
J Am Coll Cardiol. 2002 Aug 7;40(3):521-8. doi: 10.1016/s0735-1097(02)01991-5.
The study was done to determine whether radial artery applanation tonometry can be used as a noninvasive method of assessing global endothelial function. BACKGROUND; It is known that beta(2)-receptor stimulation results in endothelial release of nitric oxide. Furthermore, for over a century glyceryl trinitrate (GTN) has been known to markedly affect the arterial pressure waveform, even in the absence of significant blood pressure (BP) changes. Therefore, it was hypothesized that the change in the peripheral pressure waveform, as measured using tonometry and quantified using the augmentation index (AIx) and in response to Salbutamol (Salb), would allow assessment of global endothelial function.
The study contained three parts. In the first study, Salb (400 microg) was administered to 11 healthy subjects via inhalation after either intravenous N-omega-nitro-monomethyl-L-arginine (L-NMMA) (3 mg/kg over 5 min) or control solution (normal saline) in the supine, rested, fasted condition. The BP, heart rate and waveform responses were recorded each 5 min following Salb for 20 min. Next, GTN was given and responses recorded 5 min later. In the second study, both the reproducibility of Salb and the GTN responses were assessed in 9 subjects studied twice on separate days. In the third study, the Salb and GTN responses of 12 subjects with angiographic coronary artery disease (CAD) were compared with 10 age-matched control subjects with no atherosclerotic risk factors.
After control infusion, AIx decreased following Salb, from 50.8 +/- 4.3% to 44.8 +/- 4.2%, a change of -11.8 +/- 3.7%, p < 0.01. After L-NMMA, AIx did not significantly change following Salb (54.2 +/- 5.1% vs. 52.9 +/- 5.3%, -2.0 +/- 3.1%). The GTN-induced decreases in AIx were similar after either infusion (35.1 +/- 3.3% vs. 36.5 +/- 3.3%). Reproducibility of Salb-induced changes in AIx between studies performed on separate days was good (r = 0.80, p < 0.01). Salb-induced changes in AIx in CAD patients were significantly less compared to control subjects (-2.4 +/- 1.9% vs. -13.2 +/- 2.4%, respectively, p < 0.002). The GTN-induced changes were not significantly different (-27.6 +/- 4.2 vs. -38.9 +/- 4.4%, p = 0.07).
The peripheral arterial pressure waveform is sensitive to beta(2)-stimulation. Changes are related to nitric oxide release, are reproducible and can distinguish between clinical subject groups. Arterial waveform changes following Salb may thus provide a noninvasive method of measuring "global" arterial endothelial function.
本研究旨在确定桡动脉压平式眼压测量法是否可作为评估整体内皮功能的无创方法。背景：已知β₂受体刺激可导致内皮释放一氧化氮。此外，一个多世纪以来，人们都知道硝酸甘油（GTN）即使在无显著血压（BP）变化的情况下也会显著影响动脉压力波形。因此，有人提出假设，即使用眼压测量法测量并通过增强指数（AIx）量化的外周压力波形在对沙丁胺醇（Salb）产生反应时的变化，将有助于评估整体内皮功能。
本研究包含三个部分。在第一项研究中，11名健康受试者在仰卧、休息、禁食状态下，静脉注射N-ω-硝基-L-精氨酸甲酯（L-NMMA）（5分钟内注射3mg/kg）或对照溶液（生理盐水）后，通过吸入给予Salb（400μg）。给予Salb后，每5分钟记录一次BP、心率和波形反应，共记录20分钟。接下来，给予GTN，并在5分钟后记录反应。在第二项研究中，对9名受试者在不同日期进行了两次研究，评估了Salb和GTN反应的可重复性。在第三项研究中，将12名经血管造影确诊为冠心病（CAD）的受试者的Salb和GTN反应与10名无动脉粥样硬化危险因素、年龄匹配的对照受试者进行了比较。
对照输注后，给予Salb后AIx降低，从50.8±4.3%降至44.8±4.2%，变化为-11.8±3.7%，p<0.01。给予L-NMMA后，给予Salb后AIx无显著变化（54.2±5.1%对52.9±5.3%，-2.0±3.1%）。两种输注后GTN诱导的AIx降低相似（35.1±3.3%对36.5±3.3%）。在不同日期进行的研究中，Salb诱导的AIx变化的可重复性良好（r=0.80，p<0.01）。与对照受试者相比，CAD患者中Salb诱导的AIx变化显著较小（分别为-2.4±1.9%对-13.2±2.4%，p<0.002）。GTN诱导的变化无显著差异（-27.6±4.2对-38.9±4.4%，p=0.07）。
外周动脉压力波形对β₂刺激敏感。变化与一氧化氮释放有关，具有可重复性，且可区分临床受试者组。因此，Salb后动脉波形变化可能提供一种测量“整体”动脉内皮功能的无创方法。
