Sensitivity of the Canine Pancreatic Intraductal Pressure to Subclinical Reduction in Cholinesterase Activity

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Abstract
As a continuation of work on anticholinesterase induced pancreatitis, a study of the relationship between reduced serum cholinesterase activity and changes in pancreatic intraductal pressure was undertaken. Pharmacokinetic studies in 3 dogs revealed rapid reduction in serum cholinesterase activity following an i.v. bolus dose of the cholinesterase inhibitor O,O-diethyl-O-(2-isopropyl-6-methyl-4-pyrimidinyl)phosphorothioate. Following each dose of cholinesterase inhibitor, stable levels of cholinesterase inhibition were reached in 30 min. In 4 dogs the pancreatic duct was perfused from the tail of the ventral pancreas and intraductal pressures measured. A total of 25 mg/kg of the cholinesterase inhibitor was given in 5 mg/kg doses 30 min apart, and serum cholinesterase measured 30 min after each dose. Mean pressures were established over a 15 min interval. Linear regression analysis of 23 data points revealed a significant (P < 0.001) cumulative dose-related increase in pancreatic intraductal pressure [Pressure (cm saline) = 14.2 + 1.03 .times. Cumulative Dose (mg/kg)] and significant (P < 0.001) negative correlation between serum cholinesterase activity and intraductal pressure [Pressure (cm saline) = 48.0 - 0.057 .times. Esterase activity (mU/ml)]. In dogs, reduced cholinesterase activity may be directly related to increased pancreatic intraductal pressure and it may be a factor in the pathogenesis of pancreatitis.