Olsson G, Hjemdahl P, Rehnqvist N
Am Heart J. 1984 Sep;108(3 Pt 1):454-62. doi: 10.1016/0002-8703(84)90408-3.
Metoprolol or placebo was gradually withdrawn during 1 week in 115 patients participating in a 3-year, double-blind, postinfarction study. During the first month after withdrawal mental symptoms and increased cardiac symptoms occurred significantly more frequently in the metoprolol group. Disabling symptoms requiring reinstitution of treatment were seen in 14 of 58 in the metoprolol group vs 4 of 57 in the placebo group (p less than 0.05). In the metoprolol group, there was a rebound increase of basal heart rate and of the heart rate response to orthostatic testing during 3 weeks after withdrawal, when compared to values obtained 6 months later. In 27 patients plasma catecholamine levels were analyzed during repeated exercise tests and orthostatic provocations. Plasma norepinephrine and epinephrine responses to exercise were reduced 1 week after completion of withdrawal. At this time norepinephrine levels tended to be lower in relation to heart rate at all work loads. Our laboratory findings may be related to increased beta-adrenoceptor responsiveness, but unmasking of ischemic symptoms probably contributed to the clinical findings.
在一项为期3年的心肌梗死后双盲研究中，115名患者在1周内逐渐停用美托洛尔或安慰剂。停药后的第一个月，美托洛尔组出现精神症状和心脏症状加重的频率明显更高。美托洛尔组58名患者中有14名出现需要重新开始治疗的失能症状，而安慰剂组57名患者中有4名出现此类症状（p<0.05）。与6个月后获得的值相比，美托洛尔组在停药后3周内基础心率和直立试验时的心率反应出现反弹性增加。对27名患者在重复运动试验和直立激发试验期间分析了血浆儿茶酚胺水平。停药完成1周后，血浆去甲肾上腺素和肾上腺素对运动的反应降低。此时，在所有工作负荷下，去甲肾上腺素水平相对于心率往往较低。我们的实验室发现可能与β-肾上腺素能受体反应性增加有关，但缺血症状的暴露可能是导致临床发现的原因。
