Early peritoneal lavage with ulinastatin improves outcome and enhances multi-organ protection in a model of severe acute pancreatitis

Abstract

The aim of this study was to investigate the effect of early peritoneal lavage with ulinastatin on the outcome of a rat model of severe acute pancreatitis (SAP). A total of 80 male Wistar rats were randomly divided into the following groups: Sham-operated (C), SAP model (M), saline lavage (SL), intravenous ulinastatin (IU), early ulinastatin lavage (EUL) and late ulinastatin lavage (LUL). Intraperitoneal lavage or injection were performed immediately subsequent to the establishment of the SAP model in groups SL, IU and EUL and 3 h later in group LUL. Intraperitoneal lavage with or without ulinastatin was performed for 3 h. The survival time of the rats in groups C, M, EUL and LUL was recorded over a 12-h period and the median survival time was calculated. At 3 h after the induction of SAP, histopathological analyses were performed and the biochemical parameters of groups C, M, SL, IU and EUL were assessed. Groups EUL and LUL exhibited an increased median survival time compared with Group M, with the survival time of the rats in group EUL markedly longer than that in the group LUL rats. Group SL, IU and EUL rats were found to have reduced plasma activities of amylase, lipase, aspartate transaminase and alanine transaminase, with the biggest change observed in the group EUL rats. Furthermore, the intervention in groups SL and EUL was more effective at reducing creatinine and urea levels than that in group IU. Rats in group EUL exhibited a greater inhibition of the SAP-induced increase in troponin T levels than rats in groups SL and IU. The pathological severity scores of the pancreas, liver, kidney and lung in group EUL were significantly lower than those in groups M and better than those in groups SL and IU. In conclusion, early intraperitoneal lavage with ulinastatin significantly improves the median survival time and protects multi-organ function in an SAP model.

Keywords: antiprotease; early stage; peritoneal lavage; severe acute pancreatitis; ulinastatin.

Figure 1

Effect of early and late peritoneal lavage with ulinastatin on the survival time of rats. The survival times of rats in groups C, M, EUL and LUL (n=10 per group) was recorded over a 12-h period and median survival time was calculated. Early peritoneal ulinastatin lavage significantly improved the median survival time compared with group M (P<0.01), but late lavage did not (P>0.05). Early peritoneal ulinastatin lavage exerted a superior effect to late lavage (P<0.01). Early peritoneal ulinastatin lavage was performed immediately subsequent to the establishment of the SAP model and the late peritoneal ulinastatin lavage was performed 3 h later. All peritoneal lavage with ulinastatin was performed for 3 h. Group M, SAP model group; group EUL, early ulinastatin lavage group; group LUL, late ulinastatin lavage group; SAP, severe acute pancreatitis.

Figure 2

Effect of early peritoneal ulinastatin lavage on the activity of pancreatic enzymes (amylase and lipase). Rats in groups C, M, SL, IU and EUL (n=8 per group) were sacrificed for amylase and lipase measurements 3 h after the establishment of each model. The plasma amylase and lipase activity in group M was significantly higher than that in group C. The amylase and lipase activity in groups SL, IU and EUL was significantly reduced compared with that in group M, with the biggest reduction observed in group EUL. Results are presented as the mean ± standard deviation. ^**P<0.01 vs. group M; ^##P<0.01. Group C, control (sham-operated) group; group M, severe acute pancreatitis model group; group SL, saline lavage group; group IU, intravenous ulinastatin group; group EUL, early ulinastatin lavage group.

Figure 3

Effect of early peritoneal ulinastatin lavage on the activity of liver enzymes (ALT and AST). Rats in groups C, M, SL, IU and EUL (n=8 per group) were sacrificed for ALT and AST measurements 3 h after the establishment of each model. The plasma ALT and AST activity in group M was significantly increased compared with that in group C. The ALT and AST activity in groups SL, IU and EUL was significantly reduced compared with that in group M. The activity of ALT in group EUL was significantly lower than that in group IU, but the AST activity in group EUL was not significantly different from that in groups IU or SL. Results are presented as the mean ± standard deviation. ^**P<0.01 vs. group M; ^#P<0.05. Group C, control (sham-operated) group; group M, severe acute pancreatitis model group; group SL, saline lavage group; group IU, intravenous ulinastatin group; group EUL, early ulinastatin lavage group; ALT, alanine transaminase; AST, aspartate transaminase.

Figure 4

Effect of early peritoneal ulinastatin lavage on the CR and UR levels in the kidney. Rats in groups C, M, SL, IU and EUL (n=8 per group) were sacrificed for CR and UR measurements 3 h after the establishment of each model. The plasma CR and UR levels in group M were significantly increased compared with those in group C. The CR and UR levels in groups SL and EUL were significantly lower than those in group M and better than those in group IU. The effect in group EUL was superior to that in other groups. Results are presented as the mean ± standard deviation. ^**P<0.01 vs. group M; ^#P<0.05 and ^##P<0.01. Group C, control (sham-operated) group; group M, severe acute pancreatitis model group; group SL, saline lavage group; group IU, intravenous ulinastatin group; group EUL, early ulinastatin lavage group; CR, creatinine; UR, urea.

Figure 5

Effect of early peritoneal ulinastatin lavage on the TnT level in the heart. Rats in groups C, M, SL, IU and EUL (n=8 per group) were sacrificed for the measurement of the TnT level 3 h after the establishment of each model. The plasma TnT level in group M was significantly higher than that in group C. The plasma TnT level in groups EUL and SL was significantly lower that in groups M and IU. No significant difference was found between groups IU and M. Results are presented as the mean ± standard deviation. ^*P<0.05 and ^**P<0.01 vs. group M; ^##P<0.01. Group C, control (sham-operated) group; group M, severe acute pancreatitis model group; group SL, saline lavage group; group IU, intravenous ulinastatin group; group EUL, early ulinastatin lavage group; TnT, troponin T.