Interactions of pyridostigmine with cardiopulmonary systems and their relationships to plasma cholinesterase activity

Three dose levels of pyridostigmine (0.5, 2, and 5 mg/kg) were given iv to dogs anesthetized with sodium pentobarbital. Hemodynamic measurements made were cardiac output, blood pressure, left ventricular dP/dT, and heart rate. Pulmonary function data obtained were airway resistance, respiratory rate, and tidal volume. Activity of blood cholinesterase was also measured. Increasing doses of pyridostigmine promptly and progressively lowered the acetylcholinesterase activity of blood to a minimum of 40% of control at the 5 mg/kg dose. Airway resistance was most sensitive to the drug. Resistance increased significantly with 2 mg/kg, and the 5 mg/kg dose resulted in more than a 10-fold increase, which persisted for more than 2 hr. Tidal volume was decreased and minute volume was increased due to an increase in respiratory rate. With the higher doses, heart rate decreased and stroke volume rose sufficiently to compensate so that cardiac output was unchanged. The lowest dose produced minimal effects on both cardiovascular and respiratory systems, and since this dose is greater than that proposed for organophosphate poisoning in humans, it seems likely that this drug would not cause important effects in normal humans when used as a protective agent.