A model for distinguishing between beta1-receptors which mediate a specific effect on the heart rate and those which mediate a positively inotropic effect.

The study was conducted in six healthy male volunteers aged between 20 and 30 years. Cardiac output was determined by means of the Swan-Ganz-thermodilution-method. A control-study was carried out, during which an isoproterenolinfusion with increasing doses was given. Fifty minutes after i.v. injection of a beta-receptor-blocker the hemodynamic parameters were measured again under increasing doses of isoproterenol until the block was overcome. This study procedure was performed twice in each subject at an interval of at least 14 days. For the one study 15 mg propranolol i.v. and for the other 0,5 mg mepindolol i.v., a new beta-receptor-blocker, were injected. After i.v. injection of propranolol the dose-response-relationship-curve for the heart-rate (HR) and stroke volume (SV) describes a definite shift to the right. After mepindolol the dose-effect curve for the heart rate describes a definite shift to the right, as seen with propranolol. In contrast, only a very slight shift can be seen in respect of the SV increase, i.e. the SV and HR curves dissociate under mepindolol. The results of our study indicate, that a distinction can be made with respect to the so-called beta 1-receptors between those mediating a specific effect on the heart-rate and those mediating a mainly positive inotropic effect.