Systemic Inflammation with Multiorgan Dysfunction Is the Cause of Death in Murine Ligation-Induced Acute Pancreatitis

Background: We have previously shown that distal pancreatic duct ligation-induced acute pancreatitis in mice is associated with substantial mortality. Methods: We examined the cause of death in duct ligation-induced acute pancreatitis in mice by serial examination of multiple parameters in three experimental groups: distal pancreatic duct ligation (PD), bile duct ligation alone (BD), and sham operation (S). Results: BD and S had no mortality, while PD had 94% mortality with most deaths between days 2 and 4. Characteristics of mice with acute pancreatitis included (ANOVA; p < 0. 05): extracellular regulated kinase activation in the pancreas and lung; pancreatic neutrophil infiltration and acinar cell necrosis maximal on day 2; increased plasma cytokine and aspartate aminotransferase levels and bronchoalveolar lavage fluid neutrophil count and cytokine levels, peaked on day 3; hypotension and bradycardia were worst on day 4; pulmonary neutrophil infiltration and plasma creatinine level peaked on day 4. Liver injury evidenced by raised aspartate serum transaminase after hepatic obstruction was exacerbated by PD. Conclusions: Systemic inflammation with multiorgan dysfunction causes death in pancreatic duct ligation-induced acute pancreatitis in mice. This experimental model is a suitable experimental analogy of "early severe gallstone pancreatitis" to investigate disease pathogenesis and to evaluate novel therapeutic strategies.