Olsson G, Hjemdahl P, Rehnqvist N
Eur Heart J. 1986 Sep;7(9):765-72. doi: 10.1093/oxfordjournals.eurheartj.a062138.
In 34 patients on double-blind postinfarction treatment with metoprolol 100-200 mg daily (N = 20) or matching placebo, the study treatment was gradually withdrawn during one week. The patients were subjected to mental stress (a modified version of Stroop's colour word conflict test) before and 1 and 12 weeks after the completion of double-blind withdrawal. This stress increased heart rate (P less than 0.001), blood pressures (P less than 0.001) and adrenaline (P = 0.003), but not noradrenaline in venous plasma. In the placebo group similar responses were evoked on all three occasions. In the metoprolol group, heart rate responses were reduced while on treatment. Following withdrawal there was no rebound increase in the heart rate response. Rather, some blockade persisted one week after withdrawal. Twelve weeks after withdrawal heart rate and blood pressure responses to mental stress were normalized. During treatment the metoprolol group had fewer ventricular arrhythmias than the placebo group. Following withdrawal, ventricular arrhythmias during stress increased in 4 patients in the metoprolol group. Plasma adrenaline levels were reduced one week after withdrawal of metoprolol treatment. Plasma noradrenaline levels did not change within either group during the follow-up period. Thus, no rebound increase in cardiovascular reactivity to mental stress was found, in contrast to our previous findings with physical stressors in similar patients participating in this study. These differences in responsiveness after metoprolol withdrawal may be related to different clearance rates for metoprolol in different tissues. Our results indicate that central, presumably supramedullary, cardiovascular control mechanisms involving beta-adrenoceptors recover at a slow rate following withdrawal.
34例接受美托洛尔每日100 - 200mg双盲心肌梗死后治疗的患者（N = 20）或匹配的安慰剂，研究治疗在一周内逐渐撤药。在双盲撤药完成前、完成后1周和12周，患者接受精神应激（Stroop色词冲突测试的改良版）。这种应激使心率（P<0.001）、血压（P<0.001）和肾上腺素（P = 0.003）升高，但静脉血浆中的去甲肾上腺素未升高。在安慰剂组，在所有三个时间点都诱发了类似的反应。在美托洛尔组，治疗期间心率反应降低。撤药后心率反应没有反跳性增加。相反，撤药一周后仍有一些阻滞作用。撤药12周后，对精神应激的心率和血压反应恢复正常。治疗期间，美托洛尔组的室性心律失常比安慰剂组少。撤药后，美托洛尔组有4例患者在应激期间室性心律失常增加。美托洛尔治疗撤药一周后血浆肾上腺素水平降低。在随访期间，两组血浆去甲肾上腺素水平均未改变。因此，与我们之前在参与本研究的类似患者中对物理应激源的研究结果相反，未发现对精神应激的心血管反应性有反跳性增加。美托洛尔撤药后反应性的这些差异可能与美托洛尔在不同组织中的清除率不同有关。我们的结果表明，涉及β-肾上腺素能受体的中枢（可能是髓质以上）心血管控制机制在撤药后恢复缓慢。
