Comparisons of the inotropic effects of the beta 1-adrenoceptor partial agonists SL 75.177.10 and ICI 118,587 with digoxin on the intact canine heart.
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 three 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 micrograms/kg) increased peak (+) dP/dt by 3176 +/- 363 mm Hg/s (p less than 0.005) and the slope of the end-systolic pressure/end-systolic diameter relation rose by 190% above the control value (p less than 0.01). These changes were significantly greater than after digoxin (100 micrograms/kg) which increased these indexes, respectively, by 2132 +/- 248 mm Hg/s (p less than 0.003) and by 31 +/- 4% (p less than 0.05). SL 75.177.10 (200 micrograms/kg) also increased dP/dt, but significantly less than did digoxin or ICI 118,587 (+428 +/- 105 mm Hg/s; p less than 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 less than 0.01), neither SL 75.177.10 nor digoxin modified this phase of the cardiac cycle. Finally, 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.(ABSTRACT TRUNCATED AT 250 WORDS)
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D015784:Betaxolol / Q000031:analogs & derivatives*; D001794:Blood Pressure / Q000187:drug effects; D004077:Digoxin / Q000494:pharmacology*; D004280:Dobutamine / Q000494:pharmacology; D004285:Dogs; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects*; D011412:Propanolamines / Q000494:pharmacology*; D017307:Xamoterol
D000318:Adrenergic beta-Agonists; D011412:Propanolamines; D004280:Dobutamine; D004077:Digoxin; D017307:Xamoterol; C042399:SL 75177-10; D015784:Betaxolol