Beta adrenergic blockade with propranolol in conscious euthyroid and thyrotoxic calves: Dosage requirements and effects on heart rate and left ventricular performance

The effects of acute beta adrenergic blockade were studied in nine calves which had been instrumented with sonomicrometer crystals and pressure transducers before and after treatment with thyroxine (200 μg/kg) for 14 days. The adequacy of beta adrenergic blockade was determined using graded doses of isoproterenol. The results indicated that beta adrenergic blockade had no significant effect on heart rate, left ventricular dimensions or contractile performance in either thyroid state, However, the average dose of propranolol required to achieve beta adrenergic blockade was increased two to three times by thyroxine treatment. Consequently, the kinetics of propranolol disposition were determined in nine animals after a single i.v. dose of the drug. Also, propranolol was administered to four animals by continuous i.v. infusions at graded dosages to produce a range of serum concentrations in each animal. The amount of isoproterenol required to increase the heart rate by 25 beats/min was determined at each dosage level. It was found that in thyrotoxic animals two to three times higher serum propranolol concentrations were required to block challenge doses of isoproterenol. This could not be explained by changes in the disposition of propranolol. The possibility that there are larger numbers of functionally inactive (uncoupled) beta adrenergic receptors in thyrotoxic myocardium is discussed.