Comparisons of the Inotropic Effects of the β1Adrenoceptor Partial Agonists SL 75.177.10 and ICI 118,587 with Digoxin on the Intact Canine Heart

Publisher Website
Google Scholar
Abstract
The effects of the .beta.1-adrenoceptor partial agonists ICI 118,587 (xamoterol) and SL 75.177.10 on the left ventricular inotropic state and relaxation rate were compared with those of digoxin in open-chest dogs. These agents were administered to 3 separate groups of dogs (5, 6 and 7 dogs, respectively). In each animal, the inotropic effects were assessed at fixed heart rate (atrial pacing) and at similar end-diastolic left ventricular diameter. Under these controlled conditions, ICI 118,587 (200 .mu.g/kg) increased peak (+) dP[pressure]/dt by 3176 .+-. 363 mm Hg/s (P < 0.005) and the slope of the end-systolic pressure/end-systolic diameter relation rose by 190% above the control value (P < 0.01). These changes were significantly greater than after digoxin (100 .mu.g/kg) which increased these indexes, respectively, by 2132 .+-. 248 mm Hg/s (P < 0.003) and by 31 .+-. 4% (P < 0.05). SL 75.177.10 (200 .mu.g/kg) also increased dP/dt, but significantly less than did digoxin or ICI 118,587 (+428 .+-. 105 mm Hg/s; P < 0.007); the increase in end-systolic pressure/diameter slope was not different from that observed after digoxin. In contrast to ICI 118,587 which accelerated isovolumic relaxation (-7.6 ms in time constant of isovolumic pressure fall; P < 0.01), neither SL 75.177.10 nor digoxin modified this phase of the cardiac cycle. At the dose used in the study, digoxin induced ventricular arrhythmias in all animals, a side effect which was never observed after ICI 118,587 or SL 75.177.10. ICI 118587 is evidently a more powerful, positive inotropic agent than digoxin; SL 75.177.10 appears weaker than the glycoside, although at clinical doses of digoxin, the difference might not be significant.