Boutelant S, Lechat P, Komajda M, Isnard R, Salloum J, Gagey S, Bertholon J F, Grosgogeat Y
Service de pharmacologie, hôpital Pitié-Salpêtrière, Paris.
Arch Mal Coeur Vaiss. 1992 Jun;85(6):863-70.
The results of several studies, mostly without controls, have suggested that betablockers, administered at progressively increasing doses, may be beneficial in cardiac failure. Based on this hypothesis, betablockers with a peripheral vasodilator effect, such as Nebivolol, could be particularly valuable in this indication. A preliminary study of its tolerance, haemodynamic and neurohormonal effects was carried out with a noninvasive methodology in 12 patients with cardiac failure in sinus rhythm, 8 men and 4 women (average age 53 +/- 12 years), all of whom had Class III or IV symptoms according to the NYHA Classification. The protocol had 2 phases: the first was an open phase during which Nebivolol was administered at a dose of 1 mg/day for 48 hours then 2.5 mg/day for 72 h. In the second phase, the patients were randomly separated into 2 groups, one to receive placebo and the other 2.5 mg for one week then 5 mg of Nebivolol for the 5 remaining weeks. The heart rate decreased significantly from 70 +/- 3 to 63 +/- 4 beats/min (p < 0.01) with Nebivolol 1 mg/day without further slowing at the 2.5 mg dosage. During the randomised phase, the heart rate remained stable in the Nebivolol group but increased to its initial value in the group given placebo. No aggravation of symptoms was observed in the Nebivolol group. No significant changes in cardiac output, parameters of cardiac loading or contractility could be demonstrated after 6 weeks' treatment. During submaximal exercise testing, plasma concentrations of catecholamines and atrial natriuretic factor tended to be higher with Nebivolol than with placebo.(ABSTRACT TRUNCATED AT 250 WORDS)
多项研究(大多无对照)结果表明,逐步增加剂量使用β受体阻滞剂可能对心力衰竭有益。基于这一假设,具有外周血管扩张作用的β受体阻滞剂,如奈必洛尔,在这一适应症中可能特别有价值。我们采用无创方法对12例窦性心律的心力衰竭患者(8例男性,4例女性,平均年龄53±12岁)进行了一项关于其耐受性、血流动力学和神经激素作用的初步研究,所有患者根据纽约心脏协会(NYHA)分级均有Ⅲ级或Ⅳ级症状。研究方案有两个阶段:第一阶段为开放期,在此期间,奈必洛尔以1毫克/天的剂量给药48小时,然后以2.5毫克/天的剂量给药72小时。在第二阶段,患者被随机分为两组,一组接受安慰剂,另一组先服用2.5毫克一周,然后在剩余的5周内服用5毫克奈必洛尔。服用1毫克/天的奈必洛尔时,心率从70±3次/分钟显著降至63±4次/分钟(p<0.01),在2.5毫克剂量时心率没有进一步减慢。在随机阶段,奈必洛尔组的心率保持稳定,而服用安慰剂的组心率增加到初始值。奈必洛尔组未观察到症状加重。治疗6周后,心输出量、心脏负荷或收缩性参数均无显著变化。在次极量运动试验期间,服用奈必洛尔时血浆儿茶酚胺和心房利钠因子的浓度往往比服用安慰剂时更高。(摘要截取自250字)