BETA-ADRENERGIC-BLOCKADE WITH PROPRANOLOL IN CONSCIOUS EUTHYROID AND THYROTOXIC CALVES - DOSAGE REQUIREMENTS AND EFFECTS ON HEART-RATE AND LEFT-VENTRICULAR PERFORMANCE

  • 1 January 1981
    • journal article
    • research article
    • Vol. 219  (2) , 394-399
Abstract
The effects of acute .beta.-adrenergic blockade were studied in 9 calves which were instrumented with sonomicrometer crystals and pressure transducers before and after treatment with tyroxine (200 .mu.g/kg) for 14 days. The adequacy of .beta.-adrenergic blockade was determined using graded doses of isoproterenol. .beta.-adrenergic blockade had no significant effect on heart rate, left ventricular dimensions or contractile performance in either thyroid state. The average dose of propranolol required to achieve .beta.-adrenergic blockade was increased 2 to 3 times by thyroxine treatment. The kinetics of propranolol disposition were determined in 9 animals after a single i.v. dose of te drug. Propranolol was administered to 4 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. In thyrotoxic animals 2 to 3 times higher serum propranolol. concentrations were required to block challenge doses of isoprotereol. 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.