The relations of lung injury after cardiopulmonary bypass and infl ammatory reaction, especially neutrophil elastase

We have proved that Sivelestat preserved lung function after cardiopulmonary bypass（ CPB） in the rabbit\nmodel. We now report the therapeutic efficacy of Sivelestat in the clinical case. From July 2005, 16 patients who\nunderwent aortic arch replacements were enrolled in this study. Diagnosis included dissected aortic aneurysm in 6\npatients, true aortic arch aneurysm in 8, and traumatic aortic arch aneurysm in 1 patient. We randomly divided these\npatients into two groups. In the Pre-Group（ Pre:n=8）, infusion of Sivelestat（ 0.2mg/kg/hr） was started before the\noperation; in the Post-Group（ Post:n=8）, it was started after the operation. Serum elastase activity, interleukin-8（ IL-8）\nlevels were measured before the operation, before cessation of CPB and at the end of operation. Blood gas analyses were\nmeasured before the operation, at one and three hours after the CPB and the next morning. Because the preoperative\nP/F ratio（ arterial PO2/FiO2） varies with each case, the value of the P/F ratio at one hour after the CPB was calculated\nfor 100%. Elastase activity of both groups were increased at the end of CPB（ Pre:8.9±10.6, Post:4.6± 3.5）, then returned\nto baseline level at end of operation（ NS）. IL-8 of both groups were increased at end of CPB, then in the Pre-Group\ndecreased to 59.3± 25.0 pg/ml, but in the Post-Group increased to 97.9±45.7 pg/ml（ p=0.09）. The P/F ratio in the Pre-\nGroup was well maintained from post CPB to next morning, but in the Post-Group was decreased three hours after the\nCPB （p<0.05）. In conclusion, these fi ndings showed that Sivelestat reduced the infl ammatory reaction associated with\ncardiopulmonary bypass, and prevented the pulmonary dysfunction caused by infl ammatory reaction.