Dose-response effects of cardioselective beta blockade in coronary artery disease.

The hemodynamic dose-response effects of intravenous acebutolol, a cardioselective beta-adrenoceptor antagonist with intrinsic sympathomimetic activity, were evaluated in 12 male subjects with angiographically confirmed coronary artery disease. At rest after a saline solution control period, four doubling intravenous boluses of acebutolol (logarithmic cumulative dosage of 20, 40, 80, and 160 mg) were injected at 4-min intervals; hemodynamic variables were recorded 2 to 4 min after each injection. Hemodynamic effects of the drug during steady-state exercise were evaluated by comparison of a control exercise period with observations made at the same workload (25W to 50W) after the maximum cumulative dose (160 mg). After the four intravenous boluses, plasma acebutolol concentrations rose in log-linear fashion and levels achieved (0.6 to 3.5 micrograms/ml) were within the range at which substantial pharmacodynamic activity is usually present (i.e., 0.02 to 0.2 microgram/ml). Compared with control measurements at rest after saline solution injection, these plasma concentrations of acebutolol resulted in a quadratic reduction in heart rate (maximum delta HR, -4 bpm) and a linear increase in pulmonary artery occluded pressure (maximum delta PAOP, +3 mm Hg) without change in systemic arterial pressure. There was a small reduction in cardiac output (delta cardiac index [CI], -0.2 l/min/m2). During steady-state supine bicycle exercise, there were significant reductions in systolic blood pressure (delta SBP, -15 mm Hg, or 9%) HR (-9 bpm or -9%), cardiac output (delta CI, -1.0 l/min/m2, or -18%), and increase in PAOP (+8 mm Hg, or +38%).(ABSTRACT TRUNCATED AT 250 WORDS)