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Modification of the Action of Propranolol on Pacemaker Automaticity and Overdrive Suppression by Reserpine 1

Recently we have described a technique to determine the action of drugs on cardiac pacemakers which measures overdrive suppression and spontaneous pacemaker activity in the isolated perfused cat heart with surgically induced heart block (1). Overdrive suppression was measured by the interval between the last ventricular beat evoked by artificial stimulation and the first idioventricular beat. Using this technique we have found that not all beta blocking agents have the same effects on pacemaker automaticity and overdrive suppression. In this regard, practolol (ICI 50, 172) a beta blocker reported to be devoid of a direct myocardial depressant action increased atrial and ventricular pacemaker rates and decreased the overdrive suppression interval (ODI), whereas propranolol slowed pacemaker rates and lengthened ODI. In addition, it was found that the d-isomer of propranolol interferes with the depressant action of the 1-isomer. It has been shown by Blinks (2) that in the acutely denervated heart adrenergic nerve terminals remain viable for up to 48 hr. Since adrenergic activity may increase the activity of atrial and ventricular pacemakers resulting in an increase in rate, it is uncertain in such acutely denervated preparations whether propranolol decreases rate and lengthens ODI by an antiadrenergic action or by direct depression of cardiac membranes. The purpose of this study was to evaluate the importance of cardiac catecholamines in the effects of d- and dl-propranolol on atrial and ventricular pacemaker rates and overdrive suppression in the acutely denervated cat heart. Materials and Methods. Cats, weighing between 2 and 3 kg were rendered unconscious with electric shock while being ventilated with 100% oxygen through a cannula inserted into the trachea under local anesthesia (procaine 1%). Heparin (1000 USP units) was injected into a femoral vein prior to the electric shock.