STUDIES ON PHYSIOLOGIC EFFECTS OF LARGE DOSES OF EPINEPHRINE

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Abstract
The intraven. minimal lethal dose of epinephrine for dogs, rabbits and guinea pigs was determined. Shock was induced in dogs given large doses of epinephrine intraven. during a 31- to 135-min. period. Dogs that recovered from the shock were again injected with a large dose of epinephrine at a later date and were found to be more resistant to the drug, as had been previously reported by Parkins and co-workers. The animals were able to survive a 2d dose that would have been lethal initially, but the physiologic effects were not different from those observed after the initial injn. A low blood pressure or a state of shock followed the termination of the 2d injn. in several cases. Animals that had previously undergone sympathetic ganglionectomy reacted much more violently to large doses of epinephrine than did intact animals. By giving dogs repeated large amts. of epinephrine, a tolerance was developed in some animals as great as 3 times the surely lethal dose. Such a high tolerance was not developed in rabbits. Decisive evidence was not found for the existence of an antihormone to epinephrine as an explanation for the high tolerance acquired to the drug by dogs. The nature of the tolerance still remains an enigma.