Majid P A, Niznick J, Nishizaki S, Morris W M, Sole M J
Department of Medicine, Baylor College of Medicine, Houston, Texas 77030.
J Cardiovasc Pharmacol. 1987 Sep;10(3):309-14.
It has been claimed that beta-adrenoceptor antagonists produce clinical improvement and increase longevity in patients with idiopathic dilated cardiomyopathy. Dilated heart is critically dependent upon adrenergic support to maintain forward output. Acute withdrawal of such support, even with small doses of beta-blockers, may worsen myocardial function sufficiently to limit their widespread use. Pindolol (P), a potent beta-adrenoceptor antagonist, possesses high intrinsic sympathomimetic activity. Administration of P to patients with dilated cardiomyopathy may protect against the effects of high circulating catecholamines and at the same time partially maintain intrinsic left ventricular function. We examined the acute hemodynamic effects of P (2.5 mg orally) in seven patients with dilated cardiomyopathy (average ejection fraction, 23%) and resting tachycardia (average, 111 beats/min). As compared to baseline values, P produced a highly significant fall in heart rate (rest, 19%, p less than 0.001; exercise, 24%, p less than 0.01), cardiac output (rest, 20%, p less than 0.01; exercise, 25%, p less than 0.001), and systemic arterial pressure (exercise only, 13%, p less than 0.05). Calculated systemic vascular resistance increased significantly at rest (17%, p less than 0.05). Pulmonary artery pressures did not change. Compared to normal subjects, baseline norepinephrine levels were markedly elevated in patients with dilated cardiomyopathy at rest and during exercise. Pindolol produced a further significant increase in norepinephrine levels. Two of seven patients became appreciably short of breath after P. Despite its substantial intrinsic sympathomimetic activity, pindolol, like other beta-adrenoreceptor antagonists, produces significant hemodynamic impairment in patients with congestive cardiomyopathy. An exaggerated norepinephrine response after the drug may, by increasing peripheral vascular resistance, lead to further deterioration in left ventricular performance.
有人声称，β-肾上腺素能受体拮抗剂可使特发性扩张型心肌病患者临床症状改善并延长寿命。扩张型心脏严重依赖肾上腺素能支持来维持前向输出。即使使用小剂量的β受体阻滞剂急性撤除这种支持，也可能使心肌功能恶化到足以限制其广泛应用的程度。吲哚洛尔（P）是一种强效β-肾上腺素能受体拮抗剂，具有高内在拟交感活性。给扩张型心肌病患者使用吲哚洛尔可能预防高循环儿茶酚胺的影响，同时部分维持左心室固有功能。我们研究了吲哚洛尔（口服2.5毫克）对7例扩张型心肌病患者（平均射血分数23%，静息时心动过速，平均111次/分钟）的急性血流动力学效应。与基线值相比，吲哚洛尔使心率显著下降（静息时下降19%，p<0.001；运动时下降24%，p<0.01），心输出量下降（静息时下降20%，p<0.01；运动时下降25%，p<0.001），全身动脉压仅在运动时下降（13%，p<0.05）。计算得出的全身血管阻力在静息时显著增加（17%，p<0.05）。肺动脉压未改变。与正常受试者相比，扩张型心肌病患者静息和运动时的基线去甲肾上腺素水平明显升高。吲哚洛尔使去甲肾上腺素水平进一步显著升高。7例患者中有2例在服用吲哚洛尔后明显气短。尽管吲哚洛尔具有显著的内在拟交感活性，但与其他β-肾上腺素能受体拮抗剂一样，它会使充血性心肌病患者出现显著的血流动力学损害。用药后去甲肾上腺素反应过度可能通过增加外周血管阻力导致左心室功能进一步恶化。
