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

Abstract

BackgroundWe have previously shown that distal pancreatic duct ligation-induced acute pancreatitis in mice is associated with substantial mortality. MethodsWe 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). ResultsBD 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. ConclusionsSystemic 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.