Wisenbaugh T, Katz I, Davis J, Essop R, Skoularigis J, Middlemost S, Röthlisberger C, Skudicky D, Sareli P
Cardiology Department, Baragwanath Hospital, Johannesburg, South Africa.
J Am Coll Cardiol. 1993 Apr;21(5):1094-100. doi: 10.1016/0735-1097(93)90230-x.
This study examined the long-term (3-month) effects of nebivolol, a new beta-adrenergic blocking agent, on cardiac performance in patients with dilated cardiomyopathy.
Several beta-blocking drugs have been reported to have a beneficial hemodynamic effect in patients with dilated cardiomyopathy, but few data obtained in a placebo-controlled randomized study have addressed the mechanisms of improvement.
Twenty-four patients with dilated idiopathic (n = 22) or ischemic (n = 2) cardiomyopathy (ejection fraction 0.15 to 0.40) in stable New York Heart Association functional class II or III were entered into a double-blind randomized trial of nebivolol, a new, potent, selective beta 1-antagonist. Exercise time, invasive hemodynamic data (12- and 24-h monitoring) and variables of left ventricular function were examined at baseline and after 3 months of orally administered nebivolol (1 to 5 mg/day, n = 11) or placebo (n = 13).
Heart rate decreased (group mean 85 to 71 beats/min vs. 87 to 87 beats/min with placebo) and stroke volume increased significantly (group mean 43 to 55 ml vs. 42 to 43 ml) with nebivolol; decreases in systemic resistance, systemic arterial pressure, wedge pressure and pulmonary artery pressure were not significantly different from those with placebo. Similar hemodynamic results were obtained in the catheterization laboratory. Analysis of high fidelity measurements of left ventricular pressure showed a decrease in left ventricular end-diastolic pressure in the nebivolol group (group mean 21 to 15 vs. 24 to 20 mm Hg with placebo) but no change in the maximal rate of pressure development or in two variables of left ventricular relaxation (maximal negative rate of change of left ventricular pressure [dP/dtmax] and the time constant tau). Left ventricular mass decreased (p = 0.04). Despite a decrease in heart rate with nebivolol, there was a slight decrease in left ventricular end-diastolic volume (p = NS). End-systolic volume tended to decrease (p = 0.07) despite no reduction in end-systolic stress. The net result was a significant increase in ejection fraction (group mean 0.23 to 0.33 vs. 0.21 to 0.23 with placebo), presumably as a result of an increase in contractile performance. This effect was corroborated by an increase in a relatively load-independent variable of myocardial performance.
Nebivolol improved stroke volume, ejection fraction and left ventricular end-diastolic pressure, not through a measurable reduction in afterload or a lusitropic effect, but by improving systolic contractile performance.
本研究探讨新型β-肾上腺素能阻滞剂奈必洛尔对扩张型心肌病患者心脏功能的长期（3个月）影响。
据报道，几种β受体阻滞剂对扩张型心肌病患者具有有益的血流动力学效应，但在安慰剂对照随机研究中获得的数据很少涉及改善机制。
24例纽约心脏协会心功能Ⅱ级或Ⅲ级稳定的特发性扩张型心肌病（n = 22）或缺血性心肌病（n = 2）患者（射血分数0.15至0.40）进入奈必洛尔（一种新型、强效、选择性β1拮抗剂）的双盲随机试验。在基线时以及口服奈必洛尔（1至5毫克/天，n = 11）或安慰剂（n = 13）3个月后，检查运动时间、有创血流动力学数据（12小时和24小时监测）以及左心室功能变量。
使用奈必洛尔时心率下降（组均值从85次/分钟降至71次/分钟，而安慰剂组为87次/分钟至87次/分钟），每搏量显著增加（组均值从43毫升增至55毫升，而安慰剂组为42毫升至43毫升）；全身阻力、体动脉压、楔压和肺动脉压的下降与安慰剂组无显著差异。在导管实验室也获得了类似的血流动力学结果。对左心室压力的高保真测量分析显示，奈必洛尔组左心室舒张末期压力下降（组均值从21降至15，而安慰剂组为24至20毫米汞柱），但压力最大上升速率或左心室舒张的两个变量（左心室压力最大负变化率[dP/dtmax]和时间常数τ）无变化。左心室质量下降（p = 0.04）。尽管使用奈必洛尔时心率下降，但左心室舒张末期容积略有下降（p =无显著性差异）。尽管收缩末期应力没有降低，但收缩末期容积有下降趋势（p = 0.07）。最终结果是射血分数显著增加（组均值从0.23增至0.33，而安慰剂组为0.21至0.23），这可能是由于收缩性能增加所致。心肌性能的一个相对与负荷无关的变量增加证实了这一效应。
奈必洛尔改善了每搏量、射血分数和左心室舒张末期压力，不是通过可测量的后负荷降低或舒张期松弛作用，而是通过改善收缩期收缩性能。
