Burger W, Hampel C, Kaltenbach M, Hartmann A, Herrmann M, Hoffmann J A, Klepzig H
Department of Interventional Cardiology, St Georg Hospital, Leipzig, Germany.
Am J Cardiol. 2000 Jan 15;85(2):172-7. doi: 10.1016/s0002-9149(99)00648-7.
Earlier studies have reported on the potentiated muscarinic vasoconstriction of intracoronary acetylcholine after metoprolol application in patients with coronary artery disease. The present study investigated the effect of celiprolol, atenolol, and placebo on acetylcholine-induced vasomotion in patients with coronary artery disease. Furthermore, direct effects on coronary vasomotion and on hemodynamics were evaluated. Acetylcholine (intracoronary concentrations of 6.3x10(-7), 2.0x10(-6), and 6.3x10(-6) M) was given before and after double-blind celiprolol (0.30 mg/kg IV), atenolol (0.15 mg/kg IV), or placebo in 3x12 patients. Vasomotion was investigated by quantitative coronary angiography in proximal and distal segments of epicardial coronary arteries, and by the determination of the coronary resistance index based on Doppler-flow measurements. The investigated drugs had no direct affect on the diameter of the epicardial coronary arteries. However, celiprolol, in contrast to atenolol, significantly reduced systemic vascular resistance (change after atenolol: from 1,855+/-308 to 2,161+/-550 dyne s cm(-5); celiprolol: 1,691+/-435 to 1,411+/-343 dyne s cm(-5); and placebo: 1,722+/-215 to 1,710+/-213 dyne s cm(-5), p<0.001) and the coronary resistance index (change after atenolol: 2.52+/-3.58 to 2.86+/-4.24; celiprolol: 2.70+/-1.55 to 2.49+/-2.26; and placebo: 1.97+/-1.35 to 1.92+/-1.25, p<0.01). Celiprolol, atenolol, and placebo did not have different effects on acetylcholine-induced coronary vasomotion of epicardial conductance vessels (diminution of proximal lumen diameter before/after atenolol: 0.42+/-0.39/0.44+/-0.39 mm; celiprolol: 0.32+/-0.26/0.30+/-0.24 mm; and placebo: 0.36+/-0.29/0.43+/-0.40 mm) and of coronary resistance vessels (reduction of coronary resistance index before/after atenolol: 1.95 +/-4.74/ 1.92+/-3.74; celiprolol: 0.98+/-0.73/1.41+/-1.50; and placebo: 1.16+/-1.29/1.16+/-1.04). In contrast to atenolol, celiprolol possesses vasodilative properties in systemic and coronary resistance vessels. There was no direct effect on the diameter of conductance vessels. Acetylcholine-induced coronary vasomotion both in conductance and resistance vessels was not influenced by the beta blockers that were studied. This suggests that atenolol and celiprolol do not influence endothelium-dependent, nitric oxide related vasomotion.
早期研究报道了在冠心病患者中应用美托洛尔后冠状动脉内乙酰胆碱引起的毒蕈碱样血管收缩增强。本研究调查了塞利洛尔、阿替洛尔和安慰剂对冠心病患者乙酰胆碱诱导的血管运动的影响。此外,还评估了对冠状动脉血管运动和血流动力学的直接影响。在3×12例患者中,双盲给予塞利洛尔(0.30mg/kg静脉注射)、阿替洛尔(0.15mg/kg静脉注射)或安慰剂前后,给予乙酰胆碱(冠状动脉内浓度为6.3×10⁻⁷、2.0×10⁻⁶和6.3×10⁻⁶M)。通过定量冠状动脉造影研究心外膜冠状动脉近端和远端节段的血管运动,并基于多普勒血流测量确定冠状动脉阻力指数。所研究的药物对心外膜冠状动脉直径无直接影响。然而,与阿替洛尔相比,塞利洛尔显著降低了全身血管阻力(阿替洛尔后变化:从1855±308至2161±550达因·秒·厘米⁻⁵;塞利洛尔:1691±435至1411±343达因·秒·厘米⁻⁵;安慰剂:1722±215至1710±213达因·秒·厘米⁻⁵,p<0.001)和冠状动脉阻力指数(阿替洛尔后变化:2.52±3.58至2.86±4.24;塞利洛尔:2.70±1.55至2.49±2.26;安慰剂:1.97±1.35至1.92±1.25,p<0.01)。塞利洛尔、阿替洛尔和安慰剂对乙酰胆碱诱导的心外膜传导血管(阿替洛尔前后近端管腔直径减小:0.42±0.39/0.44±0.39mm;塞利洛尔:0.32±0.26/ 0.30±0.24mm;安慰剂:0.36±0.29/0.43±0.40mm)和冠状动脉阻力血管(阿替洛尔前后冠状动脉阻力指数降低:1.95±4.7 4/1.92±3.74;塞利洛尔:0.98±0.73/1.41±1.50;安慰剂:1.16± 1.29/1.16±1.04)的冠状动脉血管运动没有不同影响。与阿替洛尔不同,塞利洛尔在全身和冠状动脉阻力血管中具有血管舒张特性。对传导血管直径无直接影响。所研究的β受体阻滞剂不影响乙酰胆碱诱导的传导血管和阻力血管的冠状动脉血管运动。这表明阿替洛尔和塞利洛尔不影响内皮依赖性、一氧化氮相关的血管运动。