Beta-Adrenergic Blocking Effects of Propranolol.∗

The first specific beta-adrenergic blocking agent to be developed, dichloroisoproterenol (1,2), has complicating sympatnomimetic properties(3). Black and Stephenson(4) introduced pronethalol which had potent betaadrenergic blocking properties and, at least in isolated organs, had little or no sympathomimetic action. However, it was found to produce malignant tumors in mice. Further, it was not free of sympathomimetic effects, at least in the dog(5). Therefore it has been replaced with propranolol (Inderal†) (6). This investigation was designed to assess the betaadrenergic blocking effects of propranolol in the intact, anesthetized dog. Materials and methods. Dogs weighing 12.5 to 23 kg were anesthetized with a combination of morphine sulfate (2 to 3 mg/kg I.M.) and sodium pentobarbital (15 mg/kg I.V.) A catheter was introduced via an external jugular vein and placed with its tip in the right atrium. Pressure was measured with a Statham P23D strain-gauge transducer. Arterial pressure was recorded via a needle in the femoral artery. The zero reference point for pressures was half way between the dog's front and back when supine. Cardiac output was measured by the indicator dilution method. Indocyanine green dye was injected into the right atrium and blood was sampled at 38 ml/min by a Harvard pump through a Gilford cuvette densitometer. The sensitivity of the densitometer was adjusted so that a concentration of 10 mg dye/1 blood gave a deflection of 10 cm. To conserve blood volume, the sampled blood was rein-fused on completion of each dilution curve. A catheter was placed in a femoral vein for infusion of 1-epinephrine bitartrate and of isoproterenol hydrochloride. In the first series of experiments, the effects of isoproterenol on cardiac output, heart rate, stroke volume and arterial and venous pressures were measured both before and after administration of propranolol.