Comparative haemodynamic dose-response effects of intravenous propranolol and pindolol in patients with coronary heart disease

Summary

To determine whether the depression of left ventricular pumping activity associated with beta-blockade alone could be offset by a substantial degree of partial agonist activity, the haemodynamic dose-response effects of intravenous propranolol and pindolol were compared in a randomised between-group saline controlled study in twenty patients with angiographically proven coronary artery disease. The intravenous doses of propranolol (2–16 mg) and pindolol (0.2–1.6 mg) used were selected on the basis of published reports of equivalence in terms of exercise blockade of chronotropic beta-adrenoceptors. Following four intravenous boluses of each drug, administered according to a cumulative log-dosage schedule, there was a log-linear increase in the plasma concentrations of each drug. The range of plasma concentrations achieved were those which have been shown to be associated with substantial attenuation of sympathetic stimulation of cardiac beta-adrenoceptors. At rest propranolol resulted in dose-related linear reductions in heart rate and cardiac output and linear increases in left heart filling pressure and systemic vascular resistance compared with saline-controlled measurements. The only statistically significant change at rest after pindolol was a small increase in the left heart filling pressure. The calculated systemic vascular resistance was increased after propranolol but unchanged after pindolol. During supine bicycle exercise the systolic blood pressure increased less after propranolol than after saline or pindolol. The increments in all other measured haemodynamic variables during exercise were equally influenced by the two drugs. Propranolol resulted in a significantly greater depression of the relationship between left heart filling pressure and cardiac output at rest and during exercise than an equivalent beta-blocking dose of pindolol. The contrasting haemodynamic profile of the two drugs is explicable by the partial agonist stimulation of the heart by pindolol directly maintaining left ventricular pumping activity and simultaneously lowering afterload by stimulating vasodilator beta₂-adrenoceptors in peripheral arteriolar resistance vessels. In patients with impairment of left ventricular function due to coronary heart disease who require intravenous beta-blocking therapy, partial agonist activity in a beta-blocking drug may be haemodynamically advantageous.