Prevention of the adverse effects of aprotinin in autologous fibrin glue.

To avoid the adverse effects of aprotinin (Apr) in autologous fibrin glue, we compared the inhibitory properties of four commercial anti-fibrinolytic agents (tranexamic acid (Tra), epsilon-aminocaproic acid (Ips), gabexate mesilate (Gab) and nafamostat mesilate (Naf)). The optimum conditions for the lysing of fibrin glue were an incubation temperature of 37 degrees C, and incubation medium containing urokinase at 100 U/ml and plasminogen at 100 mU/ml (for the washed glue), or neither (for unwashed glue). Fibrin glues without an anti-fibrinolytic agent were quickly lysed in the incubation medium, while those with an anti-fibrinolytic agent were slowly lysed dose-dependently. Naf was the most potent inhibitor and had high affinity for the glue, but the other agents were poor inhibitors and had low affinity. The inhibition potency (IP) of each agent did not correlate with hydrophobicity, but a good correlation was obtained between the remaining coefficient (RC) and hydrophobicity. Naf did not affect the adhesive strength of the glue. These results indicate that Naf is the most suitable anti-fibrinolytic agent to replace Apr.