Influence of Plasma Proteinase Inhibitors and Aprotinin on Trypsin-induced Bradykinin Release in vitro in Man

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Abstract
The consumption of kininogen (measured as kinin-releasable material) was studied in an experimental model in vitro. Analyses were made following the addition of increasing amounts of human cationic trypsin to human serum and plasma. The consumption of kininogen was correlated with the degree of saturation of the plasma proteinase inhibitors .alpha.2-macroglobulin (.alpha.2-M) and .alpha.1-proteinase inhibitor (.alpha.1-PI) with trypsin in the presence and absence of aprotinin (Trasylol). The level of kininogen fell dramatically when .alpha.2-M was saturated to 70% in spite of 90% free .alpha.1-PI. Trypsin-.alpha.2-M complexes had no effect on kininogen levels. Sixty .mu.mol/l of aprotinin, i.e., approximately 3 .times. 106 kIU/l, blocked only 60% of the trypsin-induced kininogen consumption in serum, while 15 .mu.mol/l of aprotinin blocked 100% of this consumption in plasma. With increasing concentration of aprotinin in serum, a decreasing consumption of .alpha.2-M and especially of .alpha.1-PI was observed on the addition of trypsin. The high aprotinin concentration needed to block trypsin-induced kininogen cleavage in human serum or plasma may explain the poor clinical effect of aprotinin to date in human acute pancreatitis.

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