Rousseau M F, Cheron P, Nannan M, Vincent M F, Lavenne F, Pouleur H
Ann Med Interne (Paris). 1985;136(3):247-50.
The ideal sympathomimetic derivative should possess the positive inotropic and relaxing effects of catecholamines whilst remaining free of their side-effects. Theoretically, such properties could be present in beta 1-adrenoceptor partial agonists. Xamoterol (ICI 118,587, Corwin; ISA 43 p. 100) seems to be the most promising beta 1 partial agonist. The aim of the study was to determine if the beneficial effects of Xamoterol were maintained during long term administration. Xamoterol (200 mg twice dialy) was administered to 14 patients with anterior myocardial infarction and moderate heart failure (class II-III NYHA). After 3 months' therapy, left ventricular function improved as indicated by reduction in left ventricular (LV) end-diastolic pressure (23 +/- 5 to 16 +/- 5 mm Hg; P less than 0.0005), LV end-diastolic volume (153 to 140 ml/m2; P less than 0.05) and in LV end-systolic volume especially in 11 patients with a control end-systolic volume less than 100 ml/m2 (- 15 p. 100; P less than 0.05). LV inotropic state was also enhanced as indicated by 21 p. 100 increases in EMax, the maximal LV pressure/volume ratio (P less than 0.02) and 20 p. 100 increases in the ratio end-systolic stress/ end-systolic volume (P less than 0.02). Myocardial oxygen consumption was unchanged, global lactate extraction fraction increased from 20 +/- 18 to 33 +/- 14 p. 100 (P less than 0.05) and LV alanine release was reduced (-1.7 to -0.2 muMol/min; P less than 0.05). The rate of LV pressure fall accelerated from 57 to 52 ms (P less than 0.05) and the mean diastolic wall stress was reduced by 35 p. 100 (P less than 0.05), reflecting the improvement in LV relaxation and diastolic function. Thus, the beneficial effects of Xamoterol were maintained after prolonged therapy particularly in patients with class II-III heart failure; patients in class IV benefited less from this therapy. No tachyphylaxis or side-effects were observed.
理想的拟交感神经衍生物应具有儿茶酚胺的正性肌力和舒张作用,同时又无其副作用。从理论上讲,β1肾上腺素能受体部分激动剂可能具有这些特性。扎莫特罗(ICI 118,587,Corwin;ISA 43,第100页)似乎是最有前景的β1部分激动剂。本研究的目的是确定扎莫特罗在长期给药期间是否能维持其有益作用。对14例前壁心肌梗死合并中度心力衰竭(纽约心脏病协会II - III级)患者给予扎莫特罗(每日两次,每次200毫克)。经过3个月的治疗,左心室功能得到改善,表现为左心室舒张末期压力降低(从23±5降至16±5毫米汞柱;P<0.0005),左心室舒张末期容积减少(从153降至140毫升/平方米;P<0.05),尤其是11例收缩末期容积初始小于100毫升/平方米的患者,其左心室收缩末期容积也有所减少(-15,第100页;P<0.05)。左心室收缩状态也增强,表现为最大左心室压力/容积比(EMax)增加21%(第100页;P<0.02),收缩末期应力/收缩末期容积比增加20%(P<0.02)。心肌耗氧量未改变,整体乳酸摄取率从20±18%增加到33±14%(第100页;P<0.05),左心室丙氨酸释放减少(从-1.7降至-0.2微摩尔/分钟;P<0.05)。左心室压力下降速率从57毫秒加速至52毫秒(P<0.05),平均舒张期壁应力降低35%(第100页;P<0.05),这反映了左心室舒张和舒张功能的改善。因此,扎莫特罗在长期治疗后仍能维持有益作用,尤其对于II - III级心力衰竭患者;IV级患者从该治疗中获益较少。未观察到快速耐受性或副作用。