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Dose-response effects of cardioselective beta blockade in coronary artery disease
Insights
This study investigated the hemodynamic effects of acebutolol in patients with coronary artery disease. Acebutolol demonstrated dose-dependent reductions in heart rate and cardiac output, with increased pulmonary artery occluded pressure at rest and during exercise.
Area of Science:
- Cardiovascular Pharmacology
- Clinical Hemodynamics
Background:
- Acebutolol is a cardioselective beta-blocker with intrinsic sympathomimetic activity.
- Its hemodynamic effects in patients with coronary artery disease require detailed evaluation.
Purpose of the Study:
- To assess the dose-response hemodynamic effects of intravenous acebutolol.
- To evaluate acebutolol's impact at rest and during exercise in coronary artery disease patients.
Main Methods:
- Twelve male subjects with coronary artery disease received escalating intravenous doses of acebutolol (20-160 mg).
- Hemodynamic variables were measured at rest and during steady-state exercise (25-50W).
- Plasma acebutolol concentrations were correlated with observed hemodynamic changes.
Main Results:
- Intravenous acebutolol caused a dose-dependent reduction in heart rate and cardiac output, with an increase in pulmonary artery occluded pressure at rest.
- During exercise, acebutolol significantly decreased systolic blood pressure, heart rate, and cardiac output, while increasing pulmonary artery occluded pressure.
- Achieved plasma acebutolol levels (0.6-3.5 µg/ml) were within the pharmacologically active range.
Conclusions:
- Intravenous acebutolol exerts significant hemodynamic effects in patients with coronary artery disease.
- The drug reduces cardiac workload at rest and during exercise, but with potential for increased pulmonary artery pressures.
Abstract:
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)