First-pass lung uptake of propranolol enhanced in anaesthetized dogs.

Uptake of 14C-propranolol after a single passage through the pulmonary circulation was studied in three groups of Labrador dogs using a double indicator dilution method. Uptake in conscious, ambulant animals was 53%. This increased to 81% in dogs anaesthetized with thiopentone, nitrous oxide and halothane and to 64% in dogs anaesthetized with thiopentone, nitrous oxide and fentanyl. Interaction between lipid-soluble anaesthetic agents and pulmonary endothelial cell membranes may be an important factor in increasing lung uptake of lipophilic propranolol, although alteration in pulmonary perfusion associated with a reduction in cardiac output during general anaesthesia may play a part. The pharmacological effects of propranolol administered i.v. during general anaesthesia may be unpredictable.