Department of Interventional Cardiology, Royal Papworth Hospital, Papworth Road, Cambridge Biomedical Campus, Cambridge, CB2 0AY, UK.
Division of Cardiovascular Medicine, University of Cambridge, Cambridge, UK.
BMC Cardiovasc Disord. 2021 May 1;21(1):223. doi: 10.1186/s12872-021-02030-5.
Incretin therapies appear to provide cardioprotection and improve cardiovascular outcomes in patients with diabetes, but the mechanism of this effect remains elusive. We have previously shown that glucagon-like peptide (GLP)-1 is a coronary vasodilator and we sought to investigate if this is an adenosine-mediated effect.
We recruited 41 patients having percutaneous coronary intervention (PCI) for stable angina and allocated them into four groups administering a specific study-related infusion following successful PCI: GLP-1 infusion (Group G) (n = 10); Placebo, normal saline infusion (Group P) (n = 11); GLP-1 + Theophylline infusion (Group GT) (n = 10); and Theophylline infusion (Group T) (n = 10). A pressure wire assessment of coronary distal pressure and flow velocity (thermodilution transit time-Tmn) at rest and hyperaemia was performed after PCI and repeated following the study infusion to derive basal and index of microvascular resistance (BMR and IMR).
There were no significant differences in the demographics of patients recruited to our study. Most of the patients were not diabetic. GLP-1 caused significant reduction of resting Tmn that was not attenuated by theophylline: mean delta Tmn (SD) group G - 0.23 s (0.27) versus group GT - 0.18 s (0.37), p = 0.65. Theophylline alone (group T) did not significantly alter resting flow velocity compared to group GT: delta Tmn in group T 0.04 s (0.15), p = 0.30. The resulting decrease in BMR observed in group G persisted in group GT: - 20.83 mmHg s (24.54 vs. - 21.20 mmHg s (30.41), p = 0.97. GLP-1 did not increase circulating adenosine levels in group GT more than group T: delta median adenosine - 2.0 ng/ml (- 117.1, 14.8) versus - 0.5 ng/ml (- 19.6, 9.4); p = 0.60.
The vasodilatory effect of GLP-1 is not abolished by theophylline and GLP-1 does not increase adenosine levels, indicating an adenosine-independent mechanism of GLP-1 coronary vasodilatation.
The local research ethics committee approved the study (National Research Ethics Service-NRES Committee, East of England): REC reference 14/EE/0018. The study was performed according to institutional guidelines, was registered on http://www.clinicaltrials.gov (unique identifier: NCT03502083) and the study conformed to the principles outlined in the Declaration of Helsinki.
肠降血糖素（GLP）-1 类似物似乎为糖尿病患者提供了心脏保护并改善了心血管结局，但这种作用的机制仍难以捉摸。我们之前已经证明 GLP-1 是一种冠状动脉扩张剂，我们试图研究这是否是一种通过腺嘌呤介导的效应。
我们招募了 41 名因稳定型心绞痛而行经皮冠状动脉介入治疗（PCI）的患者，并在成功 PCI 后根据特定的研究相关输液将他们分配到四个组：GLP-1 输液组（G 组）（n=10）；安慰剂，生理盐水输液组（P 组）（n=11）；GLP-1+茶碱输液组（GT 组）（n=10）；和茶碱输液组（T 组）（n=10）。在 PCI 后进行冠状动脉远端压力和血流速度（热稀释传输时间-Tmn）的压力导丝评估，并在休息和充血时进行，然后在研究输液后重复进行，以得出基础和微血管阻力指数（BMR 和 IMR）。
我们研究中招募的患者在人口统计学方面没有显著差异。大多数患者没有糖尿病。GLP-1 导致静息 Tmn 显著降低，但茶碱不能减轻这种降低：G 组的平均 Tmn 差值（SD）-0.23 秒（0.27），而 GT 组为-0.18 秒（0.37），p=0.65。与 GT 组相比，茶碱单独（T 组）并未显著改变静息流速：Tmn 差值在 T 组为 0.04 秒（0.15），p=0.30。在 G 组观察到的 BMR 降低在 GT 组中持续存在：-20.83mmHg·s（24.54 与-21.20mmHg·s（30.41），p=0.97。与 T 组相比，GT 组中 GLP-1 并未使循环腺嘌呤水平增加更多：中位数腺嘌呤差值-2.0ng/ml（-117.1，14.8）与-0.5ng/ml（-19.6，9.4）；p=0.60。
GLP-1 的血管扩张作用不会被茶碱消除，并且 GLP-1 不会增加腺嘌呤水平，表明 GLP-1 冠状动脉扩张的作用机制与腺嘌呤无关。
当地研究伦理委员会批准了这项研究（国家研究伦理服务-NRES 委员会，英格兰东部）：REC 参考号 14/EE/0018。该研究根据机构指南进行，在 http://www.clinicaltrials.gov 上进行了注册（独特标识符：NCT03502083），并符合赫尔辛基宣言中概述的原则。
