A human urinary protease inhibitor (ulinastatin) inhibits neutrophil extracellular release of elastase during cardiopulmonary bypass

Objectives: To determine the benefits of a human urinary protease inhibitor (ulinastatin) on postoperative pulmonary dysfunction associated with neutrophil activation during cardiopulmonary bypass. Design: A prospective, randomized, clinical study. Setting: The study was performed at Keio University Hospital, Tokyo. Participants: Eighteen adult patients scheduled for primary cardiac surgery. Interventions: The patients were randomly assigned either to the control group (n = 8) or to the group (n = 10) receiving ulinastatin (600,000 U in total). Measurements and Main Results: Human neutrophil ability to release elastase in response to N- formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP) in vitro was measured before and after cardiopulmonary bypass, together with plasma levels of neutrophil elastase complex, interleukin-8, and C3a. Intrapulmonary shunt fraction was then calculated. Neutrophil elastase release in response to fMLP significantly increased in the control group, but remained unchanged in the ulinastatin group. In addition, ulinastatin minimized the increase of plasma neutrophil elastase, independently of the production of interleukin-8 or C3a. Simultaneously, ulinastatin ameliorated the increase of intrapulmonary shunt, which was correlated with extracellular elastase release. Conclusions: Ulinastatin attenuated the elevation of fMLP-induced elastase release, which was associated with the deterioration of gas exchange during cardiopulmonary bypass. The administration of this agent has a potential to lessen the risk of postperfusion lung injury.