Correlation of trypsin-plasma inhibitor complexes with mortality in experimental pancreatitis in rats

Abstract

Activation of trypsinogen in acute pancreatitis results in subsequent increases in plasma levels of trypsin bound to the inhibitors α₁-protease inhibitor (α₁-PI) and α-macroglobulin (α-M). It seems logical to speculate that plasma levels of these inhibitor-bound forms of trypsin may reflect the degree of intrapancreatic zymogen activation and that determination of such parameters may be of diagnostic and prognostic value. In order to test this hypothesis, the concentrations of trypsinogen and of trypsin bound to α₁-PI have been determined in serial plasma samples from rats who died (N=7) and survived (N=5) following induction of pancreatitis with taurocholate. Since the other major reaction product of active trypsin in plasma, α-macroglobulin-bound trypsin, cannot be measured directly, the plasma levels of trypsin-like amidase activity were determined to estimate the concentration of trypsin-α-M complex. Shortly after induction of pancreatitis, elevated levels of trypsinogen were present in plasma, but no α₁-PI-bound trypsin could be detected. Trypsin-α₁-PI complex continuously increased over the time course of pancreatitis in animals that died. In contrast, the plasma levels of trypsin-α₁-PI complex were lower in animals that survived, peaked around 15 hr postinduction at levels (182±53 ng/ml) significantly lower than those in dying animals (543±346 ng/ml), and fell during the following 48 hr. There was a significant correlation between plasma trypsin-like amidase activity and plasma α₁-PI-bound trypsin. Our data demonstrate that the concentration of activated forms of plasma trypsin in the bloodstream are correlated with mortality in experimental pancreatitis.