Influence of anticholinesterase on distribution of ventilation and gas exchange

This project was designed to titrate the influence of pyridostigmine injected intraarterially on pulmonary resistance and gas exchange in pigs and dogs. Pyridostigmine at 1 mg/kg reduced red blood cell cholinesterase activity 28-35% that was not significantly reduced further with doses up to 9 mg/kg. Plasma cholinesterase was reduced by 80% in the dog and 40% in the pig with 1 mg/kg of pyridostigmine and with 3 mg/kg it was reduced to 40% in the pig and 10% in the dog. Higher doses had no further significant effect. Breathing resistance (cm H2O/l/s) in the pig was doubled as a linear function with 9 mg/kg pyridostigmine. In the dog, breathing resistance went to a maximum of 8 cm H2O/l/s from a control value of 1 cm H2O/l/s with 3 mg/kg of pyridostigmine but did not go higher with doses up to 9 mg/kg. PaO2 was reduced by approximately 20% in the pig and 15% in the dog with pyridostigmine doses of 6-9 mg/kg. These experiments indicate that significant alterations in pulmonary function do not occur until acute dosages in the range of 3-6 mg/kg are reached. Furthermore, acute administration of large doses of pyridostigmine results in salivation and gastrointestinal stimulation well in advance of any impairment of respiratory function.