Bolli R, Brandon T A, Fisher D J, Fernandez G C, Miller R R
Am Heart J. 1983 Nov;106(5 Pt 1):1014-23. doi: 10.1016/0002-8703(83)90646-4.
Recent experimental and clinical data have stimulated interest in the use of alpha-adrenergic antagonists in acute myocardial infarction. We evaluated nicergoline, a new relatively selective alpha 1-antagonist which uniquely lowers heart rate. Open-chest dogs, randomized to control (n = 25) or intravenously treated group (n = 20; 0.5 mg/kg bolus, then 0.10 to 0.15 mg/kg/min), underwent coronary artery occlusion (CAO) followed after 25 minutes by coronary artery reperfusion (CAR). Nicergoline decreased heart rate by 47 +/- 5 bpm and mean aortic pressure by 39 +/- 4 mm Hg. Following CAO, nicergoline reduced total coronary collateral resistance (radiolabeled microspheres; 698 +/- 75 vs 2167 +/- 530 mm Hg/ml/min/gm, p less than 0.05), increased the ischemic zone/nonischemic zone flow ratio (0.14 +/- 0.04 vs 0.06 +/- 0.02, p less than 0.05), and reduced the rise in intramyocardial CO2 tension in the ischemic zone (mass spectrometry, p less than 0.001). Furthermore, the drug decreased the rate of ventricular tachycardia (VT; 191 +/- 13 vs 243 +/- 3 bpm, p less than 0.001) and the incidence of ventricular fibrillation (VF; 1 of 20 [5%] vs 7 of 25 [28%], p less than 0.05). Following CAR, nicergoline did not significantly reduce the incidence of VF but did lower rate (154 +/- 8 vs 212 +/- 10 bpm, p less than 0.001) and incidence (p less than 0.05) of VT. Thus nicergoline reduced severity of ischemia and afforded protection against arrhythmias induced by myocardial ischemia and reperfusion. The observed reduction in heart rate may have contributed importantly to these beneficial effects. Clinical investigation of this potentially useful vasodilator seems warranted.
近期的实验和临床数据激发了人们对α-肾上腺素能拮抗剂用于急性心肌梗死的兴趣。我们评估了尼麦角林，一种新型相对选择性α1拮抗剂，它能独特地降低心率。将开胸犬随机分为对照组（n = 25）或静脉治疗组（n = 20；0.5 mg/kg推注，然后0.10至0.15 mg/kg/分钟），进行冠状动脉闭塞（CAO），25分钟后进行冠状动脉再灌注（CAR）。尼麦角林使心率降低47±5次/分钟，平均主动脉压降低39±4 mmHg。CAO后，尼麦角林降低了总冠状动脉侧支循环阻力（放射性微球；698±75 vs 2167±530 mmHg/ml/分钟/克，p＜0.05），增加了缺血区/非缺血区血流比值（0.14±0.04 vs 0.06±0.02，p＜0.05），并降低了缺血区内心肌二氧化碳张力的升高（质谱分析，p＜0.001）。此外，该药物降低了室性心动过速（VT）的发生率（191±13 vs 243±3次/分钟，p＜0.001）和心室颤动（VF）的发生率（20例中的1例[5%] vs 25例中的7例[28%]，p＜0.05）。CAR后，尼麦角林没有显著降低VF的发生率，但确实降低了VT的发生率（154±8 vs 212±10次/分钟，p＜0.001）和发生率（p＜0.05）。因此，尼麦角林降低了缺血的严重程度，并为心肌缺血和再灌注诱发的心律失常提供了保护。观察到的心率降低可能对这些有益作用有重要贡献。对这种潜在有用的血管扩张剂进行临床研究似乎是有必要的。
