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

Zuobiao Yuan, David K. Meyerholz, Erik C. Twait, Duraisamy Kempuraj, Deborah E. Williard, Isaac Samuel

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1670-1678
Number of pages9
JournalJournal of Gastrointestinal Surgery
Volume15
Issue number10
DOIs
StatePublished - Oct 2011
Externally publishedYes

Bibliographical note

Funding Information:
Grant Support This material is based upon a work supported in part by the following research awards (to I.S.): (1) VA Merit Review Award, Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development (Biomedical Laboratory Research and Development), Washington, DC, (2) grant R01 DK-071731, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA, and (3) American Recovery and Reinvestment Act of 2009—supplemental award to NIH R01 DK-071731 (the content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Diabetes and Digestive and Kidney Diseases or the National Institutes of Health).

Keywords

  • Acute pancreatitis
  • Extracellular signal-regulated kinase
  • Mouse
  • Multiple organ dysfunction syndrome
  • Systemic inflammatory response syndrome

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