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Beta-blockade in ischaemic heart disease--influence of concomitant ISA or alpha-blockade on haemodynamic profile
Insights
Beta-blockers like propranolol can impair cardiac performance in patients with coronary artery disease. However, adding intrinsic sympathomimetic activity (ISA) or alpha-blockade, as seen with pindolol and labetalol, can attenuate these negative effects.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Beta-adrenergic receptor blockade is crucial for managing cardiovascular diseases.
- Non-selective beta-blockers can depress cardiac performance, particularly in patients with coronary artery disease.
Purpose of the Study:
- To compare the hemodynamic effects of propranolol, pindolol (with high intrinsic sympathomimetic activity), and labetalol (with alpha- and beta-blockade).
- To determine if intrinsic sympathomimetic activity or alpha-blockade can attenuate the cardiac depression caused by beta-blockade.
Main Methods:
- A randomized study involving 30 patients with stable coronary artery disease.
- Intravenous administration of logarithmic cumulative doses of propranolol, pindolol, and labetalol.
- Hemodynamic measurements at rest and during bicycle exercise.
Main Results:
- Propranolol caused dose-related reductions in cardiac output and increases in pulmonary artery occluded pressure at rest.
- Pindolol and labetalol attenuated the exercise-induced depression of cardiac output and pulmonary artery occluded pressure observed with propranolol.
- Labetalol induced vasodilation and increased cardiac output at rest.
Conclusions:
- Beta-blockers with intrinsic sympathomimetic activity or combined alpha- and beta-blockade are better tolerated in patients with ischemic heart disease.
- These findings support the use of beta-blockers with added vasodilator or ISA properties for improved cardiac performance in this patient population.
Abstract:
To test the hypothesis that the depression of cardiac performance induced by competitive blockade of sympathetic stimulation at beta-adrenoceptors could be attenuated by the addition of a high level of intrinsic sympathomimetic activity (ISA) or concomitant alpha- and beta-blockade, the haemodynamic dose-response effects of propranolol (non-cardioselective, no ISA), pindolol (non-cardioselective, high ISA) and labetalol (non-cardioselective, alpha-blocker) were compared in a randomized study of 30 patients with stable coronary artery disease. Following 4 intravenous (i.v.) doses of each drug given according to a logarithmic cumulative dosage schedule, changes in circulatory variables were measured 2-4 min following each i.v. bolus and during bicycle exercise following the maximum dose of each drug. At rest propranolol induced dose-related reductions in heart rate, cardiac output and increases in pulmonary artery occluded pressure and systemic vascular resistance. The only change in resting haemodynamic variables following pindolol was a small dose-related increase in pulmonary artery occluded pressure. Labetalol induced dose-related falls in systemic blood pressure and vascular resistance with linear increase in cardiac output and pulmonary artery occluded pressure. During exercise the depression of cardiac output and increase in pulmonary artery occluded pressure which occurred in patients randomized to propranolol was effectively attenuated in the pindolol and labetalol groups. These observations on cardiac performance following beta-blockade in ischaemic heart disease suggest a rational basis for the use of compounds with added vasodilator or intrinsic sympathomimetic properties.