Inhibition of intraluminal pancreatic enzymes with nafamostat mesilate improves clinical outcomes after hemorrhagic shock in swine

Hubert D. Kim, Darren Malinoski, Boris Borazjani, Madhukar S. Patel, Joseph Chen, Johnathan Slone, Xuan Mai T Nguyen, Earl Steward, Geert W. Schmid-Schonbein, David B. Hoyt

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Background: Recent studies suggest that intraluminal pancreatic enzymes play a major role in the initiation of the inflammatory cascade by the gut after hemorrhagic shock. Previous animal models have shown that the inhibition of enteral pancreatic enzymes with a serine protease inhibitor, nafamostat mesilate (NM), decreases leukocyte activation and transfusion requirements after hemorrhagic shock. The objective of this study was to determine whether enteroclysis with NM would improve the clinical outcomes in swine after hemorrhagic shock and intestinal hypoperfusion. Methods: Thirty-three male Yucatan minipigs weighing 25 kg to 30 kg underwent a controlled hemorrhage of 25 mL/kg with mesenteric clamp for further gut ischemia. Animals were allocated to three groups: (1) shock only (n = 15), (2) shock + enteroclysis with 100 mL/kg GoLYTELY (GL) as a carrier (n = 11), and (3) shock + enteroclysis with GL + 0.37 mmol/L NM (GL+NM, n = 7). Animals were resuscitated, recovered from anesthesia, observed for 3 days, and graded on a daily 4-point clinical scoring system. A score of 0 indicated a moribund state or early death, and a score of 4 indicated normal behavior. Results: Pigs treated with GL + NM had significantly higher mean postoperative recovery scores (3.8 ± 0.4, essentially normal behavior with no early deaths) compared with animals within the shock only and shock + GL groups (2.1 ± 1 with one early death and 2.2 ± 1.2 with two early deaths, respectively, analysis of variance p <0.003). Conclusion: The inhibition of intraluminal pancreatic enzymes using enteroclysis with the serine protease inhibitor, NM, after hemorrhagic shock significantly improves the clinical outcome.

Original languageEnglish (US)
Pages (from-to)1078-1082
Number of pages5
JournalJournal of Trauma - Injury, Infection and Critical Care
Volume68
Issue number5
DOIs
StatePublished - May 2010
Externally publishedYes

Fingerprint

Hemorrhagic Shock
Swine
Shock
Enzymes
Serine Proteinase Inhibitors
Leukocyte Transfusion
Miniature Swine
Small Intestine
Inhibition (Psychology)
nafamostat
Analysis of Variance
Ischemia
Anesthesia
Animal Models
Hemorrhage

Keywords

  • Hemorrhagic shock
  • Organ failure
  • Pancreatic enzymes

ASJC Scopus subject areas

  • Surgery
  • Critical Care and Intensive Care Medicine

Cite this

Inhibition of intraluminal pancreatic enzymes with nafamostat mesilate improves clinical outcomes after hemorrhagic shock in swine. / Kim, Hubert D.; Malinoski, Darren; Borazjani, Boris; Patel, Madhukar S.; Chen, Joseph; Slone, Johnathan; Nguyen, Xuan Mai T; Steward, Earl; Schmid-Schonbein, Geert W.; Hoyt, David B.

In: Journal of Trauma - Injury, Infection and Critical Care, Vol. 68, No. 5, 05.2010, p. 1078-1082.

Research output: Contribution to journalArticle

Kim, Hubert D. ; Malinoski, Darren ; Borazjani, Boris ; Patel, Madhukar S. ; Chen, Joseph ; Slone, Johnathan ; Nguyen, Xuan Mai T ; Steward, Earl ; Schmid-Schonbein, Geert W. ; Hoyt, David B. / Inhibition of intraluminal pancreatic enzymes with nafamostat mesilate improves clinical outcomes after hemorrhagic shock in swine. In: Journal of Trauma - Injury, Infection and Critical Care. 2010 ; Vol. 68, No. 5. pp. 1078-1082.
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AU - Kim, Hubert D.

AU - Malinoski, Darren

AU - Borazjani, Boris

AU - Patel, Madhukar S.

AU - Chen, Joseph

AU - Slone, Johnathan

AU - Nguyen, Xuan Mai T

AU - Steward, Earl

AU - Schmid-Schonbein, Geert W.

AU - Hoyt, David B.

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N2 - Background: Recent studies suggest that intraluminal pancreatic enzymes play a major role in the initiation of the inflammatory cascade by the gut after hemorrhagic shock. Previous animal models have shown that the inhibition of enteral pancreatic enzymes with a serine protease inhibitor, nafamostat mesilate (NM), decreases leukocyte activation and transfusion requirements after hemorrhagic shock. The objective of this study was to determine whether enteroclysis with NM would improve the clinical outcomes in swine after hemorrhagic shock and intestinal hypoperfusion. Methods: Thirty-three male Yucatan minipigs weighing 25 kg to 30 kg underwent a controlled hemorrhage of 25 mL/kg with mesenteric clamp for further gut ischemia. Animals were allocated to three groups: (1) shock only (n = 15), (2) shock + enteroclysis with 100 mL/kg GoLYTELY (GL) as a carrier (n = 11), and (3) shock + enteroclysis with GL + 0.37 mmol/L NM (GL+NM, n = 7). Animals were resuscitated, recovered from anesthesia, observed for 3 days, and graded on a daily 4-point clinical scoring system. A score of 0 indicated a moribund state or early death, and a score of 4 indicated normal behavior. Results: Pigs treated with GL + NM had significantly higher mean postoperative recovery scores (3.8 ± 0.4, essentially normal behavior with no early deaths) compared with animals within the shock only and shock + GL groups (2.1 ± 1 with one early death and 2.2 ± 1.2 with two early deaths, respectively, analysis of variance p <0.003). Conclusion: The inhibition of intraluminal pancreatic enzymes using enteroclysis with the serine protease inhibitor, NM, after hemorrhagic shock significantly improves the clinical outcome.

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KW - Organ failure

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