The Myocardial Effects of Fenoterol, Isoprenaline and Salbutamol in Normoxic and Hypoxic Sheep

Three groups, each of four sheep, were randomly allocated under blinded conditions to receive the beta-adrenoceptor agonists, salbutamol, fenoterol or isoprenaline, in doses of 0.5, 2, 8, 32 and 128 micrograms/kg intravenously at 15-minute intervals. A separate group of four animals received equal volumes of saline. Heart rate was recorded immediately prior to each drug administration and serum potassium was measured. Three to 4 days later the experiment was repeated during induced systemic hypoxia and the animals then necropsied. All the agonists produced significant increases in heart rate. During hypoxia, lower heart rates were recorded than in the normoxic experiments. Under conditions of hypoxia, all the beta-agonists produced significant hypokalaemia. Sterile saline had no effect on either heart rate or serum potassium levels. At necropsy, myocardial lesions were found in animals receiving all three beta-agonists. Subendocardial haemorrhage was consistently seen in all animals receiving fenoterol. Multifocal myonecrosis of 3-4 days duration was present in the left ventricle of all animals receiving fenoterol, in two receiving isoprenaline and in two receiving salbutamol. The lesions were most severe in the papillary muscle and were visible grossly in one animal given fenoterol and one given isoprenaline. No lesions were found in the control animals.