Urethan anesthesia protects rats against lethal endotoxemia and reduces TNF-alpha release
Anastasia Kotanidou, Augustine M. K. Choi, Richard A. Winchurch, Leo Otterbein, and Henry E. Fessler Division of Pulmonary and Critical Care Medicine and Department of Surgery, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21205-2196; and Department of Critical Care, Medical School of...
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| creator | Kotanidou, Anastasia Choi, Augustine M. K Winchurch, Richard A Otterbein, Leo Fessler, Henry E |
| description | Anastasia
Kotanidou,
Augustine M. K.
Choi,
Richard A.
Winchurch,
Leo
Otterbein, and
Henry E.
Fessler
Division of Pulmonary and Critical Care Medicine and Department of
Surgery, The Johns Hopkins Medical Institutions, Baltimore, Maryland
21205-2196; and Department of Critical Care, Medical School of
Athens University, Evangelismos Hospital, Athens, Greece GR106
76
Received 21 December 1995; accepted in final form 17 June 1996.
Kotanidou, Anastasia, Augustine M. K. Choi, Richard A. Winchurch, Leo Otterbein, and Henry E. Fessler. Urethan anesthesia protects rats against lethal endotoxemia and reduces TNF- release. J. Appl. Physiol. 81(5):
2304-2311, 1996. Urethan is a commonly used animal
anesthetic for nonrecovery laboratory surgery. However, urethan has
diverse biological effects that may complicate the interpretation of
experimental findings. This study examined the effect of urethan on the
response to an intravenous bolus of lipopolysaccharide (LPS; 30 mg/kg)
in rats. In instrumented rats, urethan (1.2 gm/kg ip) completely
prevented the fall in arterial pressure immediately after LPS
administration but did not prevent late cardiovascular collapse. In
uninstrumented rats, urethan also attenuated indexes of organ injury
measured 4 h after LPS administration, including mural bowel
hemorrhage, hemoconcentration, hypoglycemia, metabolic acidosis, and
lung myeloperoxidase activity, a measure of neutrophil sequestration.
The peak increase in tumor necrosis factor- (TNF- ) 90 min after
LPS administration was reduced 88% by urethan (2,060 ± 316 vs.
16,934 ± 847 pg/ml; P |
| doi_str_mv | 10.1152/jappl.1996.81.5.2304 |
| format | Article |
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Kotanidou,
Augustine M. K.
Choi,
Richard A.
Winchurch,
Leo
Otterbein, and
Henry E.
Fessler
Division of Pulmonary and Critical Care Medicine and Department of
Surgery, The Johns Hopkins Medical Institutions, Baltimore, Maryland
21205-2196; and Department of Critical Care, Medical School of
Athens University, Evangelismos Hospital, Athens, Greece GR106
76
Received 21 December 1995; accepted in final form 17 June 1996.
Kotanidou, Anastasia, Augustine M. K. Choi, Richard A. Winchurch, Leo Otterbein, and Henry E. Fessler. Urethan anesthesia protects rats against lethal endotoxemia and reduces TNF- release. J. Appl. Physiol. 81(5):
2304-2311, 1996. Urethan is a commonly used animal
anesthetic for nonrecovery laboratory surgery. However, urethan has
diverse biological effects that may complicate the interpretation of
experimental findings. This study examined the effect of urethan on the
response to an intravenous bolus of lipopolysaccharide (LPS; 30 mg/kg)
in rats. In instrumented rats, urethan (1.2 gm/kg ip) completely
prevented the fall in arterial pressure immediately after LPS
administration but did not prevent late cardiovascular collapse. In
uninstrumented rats, urethan also attenuated indexes of organ injury
measured 4 h after LPS administration, including mural bowel
hemorrhage, hemoconcentration, hypoglycemia, metabolic acidosis, and
lung myeloperoxidase activity, a measure of neutrophil sequestration.
The peak increase in tumor necrosis factor- (TNF- ) 90 min after
LPS administration was reduced 88% by urethan (2,060 ± 316 vs.
16,934 ± 847 pg/ml; P < 0.001).
In uninstrumented animals, urethan at 1.2 gm/kg reduced the 90%
mortality rate of a lethal dose of LPS to 0-10% when
given up to 24 h before LPS administration but did not reduce mortality
when given 2 h after LPS. Urethan neither directly bound LPS by
Limulus assay nor inhibited
LPS-stimulated TNF- mRNA expression in cultured mouse peritoneal
macrophages, but TNF- mRNA expression was suppressed by serum from a
urethan-treated rat. Moreover, rauwolscine, which shares
2 -adrenoceptor-blocking activity with urethan, also prevented death from a subsequent 90% lethal dose LPS bolus. We conclude that urethan or its metabolites protect against LPS, in part, by reducing TNF- release and
speculate that this may be mediated by
2 -adrenoceptors. These actions
of urethan make it an undesirable anesthetic agent for in vivo studies of sepsis or LPS.
tumor necrosis factor- ; lipopolysaccharide; septic shock; ethyl
carbamate; anesthetics; rauwolscine
0161-7567/96 $5.00
Copyright © 1996 the American Physiological Society</description><identifier>ISSN: 8750-7587</identifier><identifier>EISSN: 1522-1601</identifier><identifier>DOI: 10.1152/jappl.1996.81.5.2304</identifier><identifier>PMID: 8941558</identifier><identifier>CODEN: JAPHEV</identifier><language>eng</language><publisher>Bethesda, MD: Am Physiological Soc</publisher><subject>Anesthesia, General ; Anesthetics, General ; Anesthetics. Neuromuscular blocking agents ; Animals ; Biological and medical sciences ; Blotting, Northern ; Endotoxemia - metabolism ; Endotoxemia - physiopathology ; Endotoxemia - prevention & control ; Hemodynamics - drug effects ; Indicators and Reagents ; Lipopolysaccharides - administration & dosage ; Lipopolysaccharides - pharmacology ; Medical sciences ; Neuropharmacology ; Peroxidase - metabolism ; Pharmacology. Drug treatments ; Rats ; Rats, Sprague-Dawley ; Survival ; Tumor Necrosis Factor-alpha - metabolism ; Urethane</subject><ispartof>Journal of applied physiology (1985), 1996-11, Vol.81 (5), p.2304-2311</ispartof><rights>1997 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c479t-e3be1adada0f2c921e99039be5601ec1e9e4344d702c2bffac99c4758adea79f3</citedby><cites>FETCH-LOGICAL-c479t-e3be1adada0f2c921e99039be5601ec1e9e4344d702c2bffac99c4758adea79f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,3025,27903,27904</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=2494056$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8941558$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kotanidou, Anastasia</creatorcontrib><creatorcontrib>Choi, Augustine M. K</creatorcontrib><creatorcontrib>Winchurch, Richard A</creatorcontrib><creatorcontrib>Otterbein, Leo</creatorcontrib><creatorcontrib>Fessler, Henry E</creatorcontrib><title>Urethan anesthesia protects rats against lethal endotoxemia and reduces TNF-alpha release</title><title>Journal of applied physiology (1985)</title><addtitle>J Appl Physiol (1985)</addtitle><description>Anastasia
Kotanidou,
Augustine M. K.
Choi,
Richard A.
Winchurch,
Leo
Otterbein, and
Henry E.
Fessler
Division of Pulmonary and Critical Care Medicine and Department of
Surgery, The Johns Hopkins Medical Institutions, Baltimore, Maryland
21205-2196; and Department of Critical Care, Medical School of
Athens University, Evangelismos Hospital, Athens, Greece GR106
76
Received 21 December 1995; accepted in final form 17 June 1996.
Kotanidou, Anastasia, Augustine M. K. Choi, Richard A. Winchurch, Leo Otterbein, and Henry E. Fessler. Urethan anesthesia protects rats against lethal endotoxemia and reduces TNF- release. J. Appl. Physiol. 81(5):
2304-2311, 1996. Urethan is a commonly used animal
anesthetic for nonrecovery laboratory surgery. However, urethan has
diverse biological effects that may complicate the interpretation of
experimental findings. This study examined the effect of urethan on the
response to an intravenous bolus of lipopolysaccharide (LPS; 30 mg/kg)
in rats. In instrumented rats, urethan (1.2 gm/kg ip) completely
prevented the fall in arterial pressure immediately after LPS
administration but did not prevent late cardiovascular collapse. In
uninstrumented rats, urethan also attenuated indexes of organ injury
measured 4 h after LPS administration, including mural bowel
hemorrhage, hemoconcentration, hypoglycemia, metabolic acidosis, and
lung myeloperoxidase activity, a measure of neutrophil sequestration.
The peak increase in tumor necrosis factor- (TNF- ) 90 min after
LPS administration was reduced 88% by urethan (2,060 ± 316 vs.
16,934 ± 847 pg/ml; P < 0.001).
In uninstrumented animals, urethan at 1.2 gm/kg reduced the 90%
mortality rate of a lethal dose of LPS to 0-10% when
given up to 24 h before LPS administration but did not reduce mortality
when given 2 h after LPS. Urethan neither directly bound LPS by
Limulus assay nor inhibited
LPS-stimulated TNF- mRNA expression in cultured mouse peritoneal
macrophages, but TNF- mRNA expression was suppressed by serum from a
urethan-treated rat. Moreover, rauwolscine, which shares
2 -adrenoceptor-blocking activity with urethan, also prevented death from a subsequent 90% lethal dose LPS bolus. We conclude that urethan or its metabolites protect against LPS, in part, by reducing TNF- release and
speculate that this may be mediated by
2 -adrenoceptors. These actions
of urethan make it an undesirable anesthetic agent for in vivo studies of sepsis or LPS.
tumor necrosis factor- ; lipopolysaccharide; septic shock; ethyl
carbamate; anesthetics; rauwolscine
0161-7567/96 $5.00
Copyright © 1996 the American Physiological Society</description><subject>Anesthesia, General</subject><subject>Anesthetics, General</subject><subject>Anesthetics. Neuromuscular blocking agents</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Blotting, Northern</subject><subject>Endotoxemia - metabolism</subject><subject>Endotoxemia - physiopathology</subject><subject>Endotoxemia - prevention & control</subject><subject>Hemodynamics - drug effects</subject><subject>Indicators and Reagents</subject><subject>Lipopolysaccharides - administration & dosage</subject><subject>Lipopolysaccharides - pharmacology</subject><subject>Medical sciences</subject><subject>Neuropharmacology</subject><subject>Peroxidase - metabolism</subject><subject>Pharmacology. Drug treatments</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Survival</subject><subject>Tumor Necrosis Factor-alpha - metabolism</subject><subject>Urethane</subject><issn>8750-7587</issn><issn>1522-1601</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1996</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kEFLwzAUx4Moc06_gUIPHry0Jm2yNkcRp8LQy3bwFF7T17Uja0vS4fbtTd0YeJBAQvJ-v_fIn5BbRiPGRPy4hq4zEZNyGmUsElGcUH5Gxr4Uh2xK2TkZZ6mgYSqy9JJcObemlHEu2IiMMsmZENmYfC0t9hU0ATTo-gpdDUFn2x517wILfoMV1I3rAzNwJsCmaPt2hxsPQlMEFoutRhcsPmYhmK4C_2IQHF6TixKMw5vjOSHL2cvi-S2cf76-Pz_NQ81T2YeY5Mig8IuWsZYxQylpInMU_guo_RV5wnmR0ljHeVmCltKbIoMCIZVlMiH80Ffb1jmLpepsvQG7V4yqISj1G5QaglIZU0INQXnt7qB123yDxUk6JuPr98c6OA2mtNDo2p2wmEtOxdRjDwesqlfVd21RddXe1a1pV_th8J-J_H90tjVmgbt-cE6K6ooy-QHVP5Wv</recordid><startdate>19961101</startdate><enddate>19961101</enddate><creator>Kotanidou, Anastasia</creator><creator>Choi, Augustine M. K</creator><creator>Winchurch, Richard A</creator><creator>Otterbein, Leo</creator><creator>Fessler, Henry E</creator><general>Am Physiological Soc</general><general>American Physiological Society</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>19961101</creationdate><title>Urethan anesthesia protects rats against lethal endotoxemia and reduces TNF-alpha release</title><author>Kotanidou, Anastasia ; Choi, Augustine M. K ; Winchurch, Richard A ; Otterbein, Leo ; Fessler, Henry E</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c479t-e3be1adada0f2c921e99039be5601ec1e9e4344d702c2bffac99c4758adea79f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1996</creationdate><topic>Anesthesia, General</topic><topic>Anesthetics, General</topic><topic>Anesthetics. Neuromuscular blocking agents</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Blotting, Northern</topic><topic>Endotoxemia - metabolism</topic><topic>Endotoxemia - physiopathology</topic><topic>Endotoxemia - prevention & control</topic><topic>Hemodynamics - drug effects</topic><topic>Indicators and Reagents</topic><topic>Lipopolysaccharides - administration & dosage</topic><topic>Lipopolysaccharides - pharmacology</topic><topic>Medical sciences</topic><topic>Neuropharmacology</topic><topic>Peroxidase - metabolism</topic><topic>Pharmacology. Drug treatments</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Survival</topic><topic>Tumor Necrosis Factor-alpha - metabolism</topic><topic>Urethane</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kotanidou, Anastasia</creatorcontrib><creatorcontrib>Choi, Augustine M. K</creatorcontrib><creatorcontrib>Winchurch, Richard A</creatorcontrib><creatorcontrib>Otterbein, Leo</creatorcontrib><creatorcontrib>Fessler, Henry E</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Journal of applied physiology (1985)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kotanidou, Anastasia</au><au>Choi, Augustine M. K</au><au>Winchurch, Richard A</au><au>Otterbein, Leo</au><au>Fessler, Henry E</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Urethan anesthesia protects rats against lethal endotoxemia and reduces TNF-alpha release</atitle><jtitle>Journal of applied physiology (1985)</jtitle><addtitle>J Appl Physiol (1985)</addtitle><date>1996-11-01</date><risdate>1996</risdate><volume>81</volume><issue>5</issue><spage>2304</spage><epage>2311</epage><pages>2304-2311</pages><issn>8750-7587</issn><eissn>1522-1601</eissn><coden>JAPHEV</coden><abstract>Anastasia
Kotanidou,
Augustine M. K.
Choi,
Richard A.
Winchurch,
Leo
Otterbein, and
Henry E.
Fessler
Division of Pulmonary and Critical Care Medicine and Department of
Surgery, The Johns Hopkins Medical Institutions, Baltimore, Maryland
21205-2196; and Department of Critical Care, Medical School of
Athens University, Evangelismos Hospital, Athens, Greece GR106
76
Received 21 December 1995; accepted in final form 17 June 1996.
Kotanidou, Anastasia, Augustine M. K. Choi, Richard A. Winchurch, Leo Otterbein, and Henry E. Fessler. Urethan anesthesia protects rats against lethal endotoxemia and reduces TNF- release. J. Appl. Physiol. 81(5):
2304-2311, 1996. Urethan is a commonly used animal
anesthetic for nonrecovery laboratory surgery. However, urethan has
diverse biological effects that may complicate the interpretation of
experimental findings. This study examined the effect of urethan on the
response to an intravenous bolus of lipopolysaccharide (LPS; 30 mg/kg)
in rats. In instrumented rats, urethan (1.2 gm/kg ip) completely
prevented the fall in arterial pressure immediately after LPS
administration but did not prevent late cardiovascular collapse. In
uninstrumented rats, urethan also attenuated indexes of organ injury
measured 4 h after LPS administration, including mural bowel
hemorrhage, hemoconcentration, hypoglycemia, metabolic acidosis, and
lung myeloperoxidase activity, a measure of neutrophil sequestration.
The peak increase in tumor necrosis factor- (TNF- ) 90 min after
LPS administration was reduced 88% by urethan (2,060 ± 316 vs.
16,934 ± 847 pg/ml; P < 0.001).
In uninstrumented animals, urethan at 1.2 gm/kg reduced the 90%
mortality rate of a lethal dose of LPS to 0-10% when
given up to 24 h before LPS administration but did not reduce mortality
when given 2 h after LPS. Urethan neither directly bound LPS by
Limulus assay nor inhibited
LPS-stimulated TNF- mRNA expression in cultured mouse peritoneal
macrophages, but TNF- mRNA expression was suppressed by serum from a
urethan-treated rat. Moreover, rauwolscine, which shares
2 -adrenoceptor-blocking activity with urethan, also prevented death from a subsequent 90% lethal dose LPS bolus. We conclude that urethan or its metabolites protect against LPS, in part, by reducing TNF- release and
speculate that this may be mediated by
2 -adrenoceptors. These actions
of urethan make it an undesirable anesthetic agent for in vivo studies of sepsis or LPS.
tumor necrosis factor- ; lipopolysaccharide; septic shock; ethyl
carbamate; anesthetics; rauwolscine
0161-7567/96 $5.00
Copyright © 1996 the American Physiological Society</abstract><cop>Bethesda, MD</cop><pub>Am Physiological Soc</pub><pmid>8941558</pmid><doi>10.1152/jappl.1996.81.5.2304</doi><tpages>8</tpages></addata></record> |
| fulltext | fulltext |
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| ispartof | Journal of applied physiology (1985), 1996-11, Vol.81 (5), p.2304-2311 |
| issn | 8750-7587 1522-1601 |
| language | eng |
| recordid | cdi_pascalfrancis_primary_2494056 |
| source | MEDLINE; American Physiological Society; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Anesthesia, General Anesthetics, General Anesthetics. Neuromuscular blocking agents Animals Biological and medical sciences Blotting, Northern Endotoxemia - metabolism Endotoxemia - physiopathology Endotoxemia - prevention & control Hemodynamics - drug effects Indicators and Reagents Lipopolysaccharides - administration & dosage Lipopolysaccharides - pharmacology Medical sciences Neuropharmacology Peroxidase - metabolism Pharmacology. Drug treatments Rats Rats, Sprague-Dawley Survival Tumor Necrosis Factor-alpha - metabolism Urethane |
| title | Urethan anesthesia protects rats against lethal endotoxemia and reduces TNF-alpha release |
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