Effect Of Ulinastatin On Neutrolphil Elastase In Pediatric Patients Undergoing Cardiopulmonary Bypass

Background: It has been known for many years that cardiopulmonary bypass (CPB) induces a systemic inflammatory response (SIR) in patients following cardiac surgery that can lead to major organ injury. CPB induces an acute inflammatory response, The inflammatory injury results leakage of fluid into extravascular spaces and organ dysfunction, especially in the lungs. The pathophysiology of the inflammatory injury is still incompletely understood, however, the sequestration of neutrophils in the lungs may be involved. Neutrophil activation, which incites an inflammatory response in the pulmonary vasculature, is known to be induced by IL-8, which is produced by alveolar marcrophages. IL-8 is chemokine which has chemoattractant and activating functions specific for neutrophils. IL-8 is a major neutrophil chemotactic factor in the lungs. Transvascular migration ofactivated neutrophils occurs into tissues, proteases and neutrophil elastase (NE) are released, which cause additional vascular and parenchymal damage. A human urinary protease inhibitor, Ulinastatin has been shown to inhibit the ability of neutrophils to release elastase in vitro and in vivo. However, there have been few reports concerning the effect of a human urinary protease inhibitor (Ulinastatin) on respiratory function in pediatric patients undergoing cardiopulmonary bypass. In the present study, we examined the effects of the human urinary trypsin inhibitor ulinastatin on the neutrophil elastase (NE) concentration and IL-8 concentration. To investigate whether ulinastatin pretreatment protects the respiratory function in pediatric patients undergoing cardiopulmonary bypass. Methods: Twenty-seven pediatric patients with congenital heart disease, undergoing cardiac surgery were studied. They were randomly divided into a control group (group c, n=13) and an Ulinastatin group (group U, n=14) in which patients received total 15000u/kg of Ulinastatin. Ulinastatin was given 5000u/kg at before CPB, at release of the aorta cross-clamp and immediately after CPB respectively. Arterial blood samples (2ml) were drawn at the following times: befor CPB, immediately after CPB, 1 hour after CPB, 12 hours after CPB and 24 hours after CPB. And interleukin-8 (IL-8) and NE concentrations were measured with enzyme-linked immunosorbent assay. Arterial blood was taken for gas analysis at 1 hour after CPB, 2 hours after CPB and 4 hours after CPB, and alveolar-arterial oxygen difference (P(A-a)O2) was calculated.Results: 1. IL-8 and NE concentrations before CPB did not differ between the groups. IL-8 of two groups increased after CPB, peaked 1 hour after CPB, and gradually decreased thereafter to the basal line at 12 hours after CPB. IL-8 concentration of group C at 1 hour after CPB was obviously higher than that of pre-CPB (P<0.05); But U group didn't obviously increase. IL-8 at 1 hour after CPB of group U was obviously lower than that of group C (P<0.05).2. NE of group C immediately increased after CPB, peaked at 1 hour after CPB and higher than that of pre-CPB (P<0.05), and gradually decreased thereafter to the basal line 24 hours after CPB. NE of group U at the two time point (immediately after CPB and 1 hour after CPB) was obviously lower than those of group C (P<0.05).3. P(A-a)O2 at 1 hour after CPB of group U was significantly lower than that of group C (P<0.05).but there is no significance of ventilation time between two groups. Conclusions: Ulinastatin was effective for suppressing the excessive release of Neutrophil elastase, it also suppresses the lung injury, protects the respiratory function in pediatric patients undergoing CPB.