CONTRASTING ACTIONS OF CELIPROLOL AND METOPROLOL ON CARDIAC-PERFORMANCE IN NORMAL VOLUNTEERS

A double-blind, randomized, placebo-controlled comparison of metoprolo l (50 mg) and celiprolol (200 mg) was undertaken in nine normal volunt eers. Rest and exercise (supine bicycle) hemodynamics were assessed at 0, 2, 4, 6, and 8 hours following single oral doses of medication adm inistered at weekly intervals. The influence of the ancillary pharmaco logical properties of metoprolol and celiprolol on cardiac pumping ind ices was assessed from heart rate and peak aortic acceleration (pkA - Exerdop). Following placebo, the heart rate and pkA increased progress ively with exercise duration and workload. Following metoprolol 50 mg, the heart rate (-9.7 beat/min at 75 watts exercise) and pkA decreased . The blunting of acceleration was greater at higher exercise workload s (-6.7 m/sec(2) at 75 watts exercise). Celiprolol reduced heart rate (-6.9 beat/min at 75 watts exercise) without a change in pkA. The hear t rate/pkA relationship showed significant parallel displacement, down wards after metoprolol but upwards after celiprolol. Thus, for a given heart rate increment there was a greater decrease in pkA after metopr olol compared with celiprolol. The different ancillary pharmacological profiles of metoprolol and celiprolol resulted in contrasting hemodyn amic profiles. The observed differences in the heart rate/pkA relation ships may be attributable to the peripheral actions of these agents. T he therapeutic relevance of the better maintained cardiac pumping indi ces on celiprolol for ischemic patients with impaired cardiac function warrants further investigation.