Local anesthetics reduce mortality and protect against renal and hepatic dysfunction in murine septic peritonitis

George Gallos, Dean R. Jones, Samih H. Nasr, Charles W. Emala, H. Thomas Lee

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

Background: Mortality from sepsis frequently results from multiple organ injury and dysfunction. Cecal ligation and puncture is an established murine model of septic peritonitis that produces septic shock characterized by an initial hyperinflammatory response. In addition to their anesthetic properties, local anesthetics have been shown to attenuate inflammatory responses both in vivo and in vitro. In the current study, the ability of local anesthetic infusions to protect against sepsis-induced mortality, as well as renal and hepatic dysfunction after cecal ligation and puncture, was investigated. Methods: C57BL/6 mice received mini-osmotic pumps containing saline (vehicle), 10% lidocaine, or 1% bupivacaine and were subjected to cecal ligation and puncture. Twenty-four hours after cecal ligation and puncture, renal and hepatic functions were assessed as well as markers of inflammation (proinflammatory cytokine protein and mRNA concentrations and myeloperoxidase activity). Renal apoptosis and 7-day survival was also assessed. Results: Mice treated with lidocaine or bupivacaine infusion showed improved survival and had significantly lower plasma creatinine, aspartate aminotransferase, and alanine amino-transferase concentrations compared with mice receiving vehicle alone. Significant reduction in plasma tumor necrosis factor-α and keratinocyte-derived chemokine, as well as reductions in myeloperoxidase activity, intracellular adhesion molecule-1 protein expression, mRNA concentrations of proinflammatory markers, and apoptosis were observed in renal cortices from both local anesthetic groups. Conclusions: The current data demonstrate that local anesthetic infusions confer a protective effect in mice from septic peritonitis by attenuating the hyperacute inflammatory response. This suppression resulted in improved mortality and less progression to acute kidney and liver injury and dysfunction.

Original languageEnglish (US)
Pages (from-to)902-911
Number of pages10
JournalAnesthesiology
Volume101
Issue number4
DOIs
StatePublished - Oct 2004
Externally publishedYes

Fingerprint

Local Anesthetics
Peritonitis
Punctures
Ligation
Kidney
Mortality
Liver
Bupivacaine
Lidocaine
Peroxidase
Sepsis
Apoptosis
Messenger RNA
Multiple Trauma
Septic Shock
Transferases
Aspartate Aminotransferases
Inbred C57BL Mouse
Acute Kidney Injury
Alanine

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

Local anesthetics reduce mortality and protect against renal and hepatic dysfunction in murine septic peritonitis. / Gallos, George; Jones, Dean R.; Nasr, Samih H.; Emala, Charles W.; Lee, H. Thomas.

In: Anesthesiology, Vol. 101, No. 4, 10.2004, p. 902-911.

Research output: Contribution to journalArticle

Gallos, George ; Jones, Dean R. ; Nasr, Samih H. ; Emala, Charles W. ; Lee, H. Thomas. / Local anesthetics reduce mortality and protect against renal and hepatic dysfunction in murine septic peritonitis. In: Anesthesiology. 2004 ; Vol. 101, No. 4. pp. 902-911.
@article{212c34d67bbd4a5c8ae34925c66b4c69,
title = "Local anesthetics reduce mortality and protect against renal and hepatic dysfunction in murine septic peritonitis",
abstract = "Background: Mortality from sepsis frequently results from multiple organ injury and dysfunction. Cecal ligation and puncture is an established murine model of septic peritonitis that produces septic shock characterized by an initial hyperinflammatory response. In addition to their anesthetic properties, local anesthetics have been shown to attenuate inflammatory responses both in vivo and in vitro. In the current study, the ability of local anesthetic infusions to protect against sepsis-induced mortality, as well as renal and hepatic dysfunction after cecal ligation and puncture, was investigated. Methods: C57BL/6 mice received mini-osmotic pumps containing saline (vehicle), 10{\%} lidocaine, or 1{\%} bupivacaine and were subjected to cecal ligation and puncture. Twenty-four hours after cecal ligation and puncture, renal and hepatic functions were assessed as well as markers of inflammation (proinflammatory cytokine protein and mRNA concentrations and myeloperoxidase activity). Renal apoptosis and 7-day survival was also assessed. Results: Mice treated with lidocaine or bupivacaine infusion showed improved survival and had significantly lower plasma creatinine, aspartate aminotransferase, and alanine amino-transferase concentrations compared with mice receiving vehicle alone. Significant reduction in plasma tumor necrosis factor-α and keratinocyte-derived chemokine, as well as reductions in myeloperoxidase activity, intracellular adhesion molecule-1 protein expression, mRNA concentrations of proinflammatory markers, and apoptosis were observed in renal cortices from both local anesthetic groups. Conclusions: The current data demonstrate that local anesthetic infusions confer a protective effect in mice from septic peritonitis by attenuating the hyperacute inflammatory response. This suppression resulted in improved mortality and less progression to acute kidney and liver injury and dysfunction.",
author = "George Gallos and Jones, {Dean R.} and Nasr, {Samih H.} and Emala, {Charles W.} and Lee, {H. Thomas}",
year = "2004",
month = "10",
doi = "10.1097/00000542-200410000-00015",
language = "English (US)",
volume = "101",
pages = "902--911",
journal = "Anesthesiology",
issn = "0003-3022",
publisher = "Lippincott Williams and Wilkins",
number = "4",

}

TY - JOUR

T1 - Local anesthetics reduce mortality and protect against renal and hepatic dysfunction in murine septic peritonitis

AU - Gallos, George

AU - Jones, Dean R.

AU - Nasr, Samih H.

AU - Emala, Charles W.

AU - Lee, H. Thomas

PY - 2004/10

Y1 - 2004/10

N2 - Background: Mortality from sepsis frequently results from multiple organ injury and dysfunction. Cecal ligation and puncture is an established murine model of septic peritonitis that produces septic shock characterized by an initial hyperinflammatory response. In addition to their anesthetic properties, local anesthetics have been shown to attenuate inflammatory responses both in vivo and in vitro. In the current study, the ability of local anesthetic infusions to protect against sepsis-induced mortality, as well as renal and hepatic dysfunction after cecal ligation and puncture, was investigated. Methods: C57BL/6 mice received mini-osmotic pumps containing saline (vehicle), 10% lidocaine, or 1% bupivacaine and were subjected to cecal ligation and puncture. Twenty-four hours after cecal ligation and puncture, renal and hepatic functions were assessed as well as markers of inflammation (proinflammatory cytokine protein and mRNA concentrations and myeloperoxidase activity). Renal apoptosis and 7-day survival was also assessed. Results: Mice treated with lidocaine or bupivacaine infusion showed improved survival and had significantly lower plasma creatinine, aspartate aminotransferase, and alanine amino-transferase concentrations compared with mice receiving vehicle alone. Significant reduction in plasma tumor necrosis factor-α and keratinocyte-derived chemokine, as well as reductions in myeloperoxidase activity, intracellular adhesion molecule-1 protein expression, mRNA concentrations of proinflammatory markers, and apoptosis were observed in renal cortices from both local anesthetic groups. Conclusions: The current data demonstrate that local anesthetic infusions confer a protective effect in mice from septic peritonitis by attenuating the hyperacute inflammatory response. This suppression resulted in improved mortality and less progression to acute kidney and liver injury and dysfunction.

AB - Background: Mortality from sepsis frequently results from multiple organ injury and dysfunction. Cecal ligation and puncture is an established murine model of septic peritonitis that produces septic shock characterized by an initial hyperinflammatory response. In addition to their anesthetic properties, local anesthetics have been shown to attenuate inflammatory responses both in vivo and in vitro. In the current study, the ability of local anesthetic infusions to protect against sepsis-induced mortality, as well as renal and hepatic dysfunction after cecal ligation and puncture, was investigated. Methods: C57BL/6 mice received mini-osmotic pumps containing saline (vehicle), 10% lidocaine, or 1% bupivacaine and were subjected to cecal ligation and puncture. Twenty-four hours after cecal ligation and puncture, renal and hepatic functions were assessed as well as markers of inflammation (proinflammatory cytokine protein and mRNA concentrations and myeloperoxidase activity). Renal apoptosis and 7-day survival was also assessed. Results: Mice treated with lidocaine or bupivacaine infusion showed improved survival and had significantly lower plasma creatinine, aspartate aminotransferase, and alanine amino-transferase concentrations compared with mice receiving vehicle alone. Significant reduction in plasma tumor necrosis factor-α and keratinocyte-derived chemokine, as well as reductions in myeloperoxidase activity, intracellular adhesion molecule-1 protein expression, mRNA concentrations of proinflammatory markers, and apoptosis were observed in renal cortices from both local anesthetic groups. Conclusions: The current data demonstrate that local anesthetic infusions confer a protective effect in mice from septic peritonitis by attenuating the hyperacute inflammatory response. This suppression resulted in improved mortality and less progression to acute kidney and liver injury and dysfunction.

UR - http://www.scopus.com/inward/record.url?scp=4644261782&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=4644261782&partnerID=8YFLogxK

U2 - 10.1097/00000542-200410000-00015

DO - 10.1097/00000542-200410000-00015

M3 - Article

C2 - 15448523

AN - SCOPUS:4644261782

VL - 101

SP - 902

EP - 911

JO - Anesthesiology

JF - Anesthesiology

SN - 0003-3022

IS - 4

ER -