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The acute haemodynamic effects of beta-blockade with propranolol and combined alpha-blockade and beta-blockade with labetalol were compared in a randomised study in 12 patients with coronary artery disease proved by angiography. Propranolol induced significantly greater depression of left ventricular function both at rest and during exercise than labetalol. This difference was probably attributable to the vasodilator activity of labetalol and the associated reduction in afterload offsetting the haemodynamic disadvantages of blockade of cardiac beta-adrenoceptors alone. The haemodynamic advantages of combined alpha-blockade and beta-blockade over beta-blockade alone may thus have therapeutic implications for the use of these treatments in patients with coronary heart disease.

On the hypothesis that the addition of alpha-blockade would mitigate the haemodynamic disadvantages of beta-blockade alone in the early stages of uncomplicated acute myocardial infarction, 15 patients were studied during the intravenous infusion of labetalol (0.5 mg/kg/h). The mean systemic arterial pressure was reduced by an average of 15 mm Hg. In the nine patients haemodynamically evaluated, the cardiac output (thermal dilution) was reduced without change in the heart rate or left heart filling pressure (pulmonary artery occluded pressure); left ventricular stroke work was significantly decreased. The reduction in these major determinants of myocardial oxygen consumption suggests that the combination of alpha- and beta-blockade may be haemodynamically advantageous in normotensive patients in the early stages of uncomplicated acute myocardial infarction.

The comparative haemodynamic dose-response effects of beta- (propranolol) or alpha- plus beta-blockade (labetalol) were evaluated in a randomised between-group study of 16 patients with an uncomplicated acute myocardial infarction. In equivalent beta-blocking doses both drugs equally reduced myocardial stroke work index and presumably myocardial oxygen requirements. However, although propranolol reduced heart rate and cardiac output, these haemodynamic changes were accompanied by an augmentation of systemic vascular resistance. In contrast, labetalol reduced heart rate, cardiac output without change in systemic vascular resistance. Moreover, concomitant alpha- and beta-blockade with labetalol resulted in lesser depression of cardiac output at equivalent beta-blocking doses to propranolol. These results suggest that the addition of alpha to beta-blockade may attenuate some of the adverse reflex circulatory consequences of pure beta-blockade; the usefulness of this pharmacological approach to the manipulation of the circulation in the early post-infarction period merits further study.

The immediate haemodynamic dose response effects of beta blockade (propranolol: 2 to 16 mg) were compared with those of combined alpha beta blockade (labetalol: 10 to 80 mg) in a randomised study of 20 patients with stable angina pectoris. After control measurements, the circulatory changes induced by four logarithmically cumulative intravenous boluses of each drug in equivalent beta blocking doses were evaluated at rest, after which comparison of the effects of the maximum cumulative dose of each was undertaken during a four minute period of supine bicycle exercise. Propranolol, at rest, induced significant dose related reductions in heart rate and cardiac output, with reciprocal increases in the systemic vascular resistance and pulmonary artery occluded pressure; systemic arterial pressure was unchanged. Labetalol was followed by significant dose related decreases in systemic blood pressure and vascular resistance associated with a significant increase in cardiac output; heart rate and pulmonary artery occluded pressure were unchanged. The slope of the left ventricular pumping function curve relating output to filling pressure from rest to exercise was significantly depressed by propranolol but unchanged after labetalol. The less deleterious effects on left ventricular haemodynamic performance after alpha beta blockade in contrast to beta blockade alone in ischaemic heart disease may be attributable to the concomitant reduction in left ventricular afterload associated with the alpha blocking activity of labetalol.

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.

The haemodynamic consequences of combined alpha- and beta-adrenoceptor blockade with intravenous labetalol were evaluated in 21 males with either high (n = 6), normal (n = 9) or low (n = 6) systemic arterial pressure, 4-17 hours after acute myocardial infarction without heart failure. Labetalol 190 +/- 18 mg (range 62-300 mg) infusion resulted in dose-related falls in systolic (P less than 0.01) and diastolic (P less than 0.05) arterial pressure in all patients. The rate of pressure reduction per mg of infused labetalol was directly proportional to the control systolic arterial pressure. Cardiac output (thermodilution) was reduced (P less than 0.05) with low dose labetalol (39 +/- 5 mg) without change on continued infusion. Left heart filling pressure (pulmonary artery occluded pressure) was unchanged throughout infusion in all patients. In conclusion, the vasodilating properties of labetalol appeared to offset the beta-blocker induced depression of cardiac function. The increased sensitivity to the effects of labetalol in those patients with hypertension may be related to excessive alpha-adrenoceptor mediated vasoconstriction in this patient group.