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.