Comparative Haemodynamic Studies with Mepindolol-Sulphate(SH E 222) and Propranolol (Inderal®,Dociton®) in the Isoproterenol Test

Abstract

The haemodynamic effects of a β-receptor blockade with mepindolol-sulphate and propranolol were studied under basal conditions and under an increasing dose of isoproterenol in 6 subjects aged between 25 and 30 years.

Special attention was paid to possible differences between the two substances as regards their affinity for the various β ₁ and β ₂ -receptors. The cardiac output (HMV) was determined with the aid of the Swan-Ganz-thermodilution method, the blood pressure was measured wet. The results led to the following conclusions:

A decrease in the heart rate (HR) occurs under basal conditions after propranolol, but not after administration of mepindolol-sulphate. The lack of an effect of mepindolol-sulphate on the HR at rest can be explained by its intrinsic activity.

A reduction of the stroke volume (SV) occurs under basal conditions after propranolol, whereas no effect on the SV was observed under mepindolol-sulphate. Three properties of mepindolol-sulphate are responsible for this lack of effect on the S V, namely its only slight quinidine-like effect compared with propranolol, its intrinsic activity and its only slight affinity for the inotropism receptors at the heart.

An infusion of isoproterenol leads to a decrease in the pulmonary capillary pressures (Pc pressures). This effect can be competitively suppressed both with propranolol and with mepindolol-sulphate. This effect has been explained by the fact that isoproterenol leads to dilatation of the venous capacity vessels as a result of stimulation of the β ₂ -receptors in the periphery. Blockade of the β ₂ -receptors can prevent this dilatation.

The affinities of propranolol for the frequency and inotropism receptors at the heart and for the β ₂ -receptors in the peripheral vessels are of the same magnitude. In contrast to this, the affinity of mepindolol-sulphate for the inotropism receptors at the heart is considerably less than for the frequency receptors and the β ₂ -receptors in the periphery.