Low-dose terlipressin improves systemic and splanchnic hemodynamics in fluid-challenged endotoxic rats

OBJECTIVEVasopressin has been used to treat arterial hypotension associated with hyperdynamic vasoplegic states, but detrimental effects on splanchnic circulation have been reported. We tested the effects of a low-dose vasopressin analogue, terlipressin (6 μg/kg), on systemic and splanchnic hemodyna...

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Veröffentlicht in:Critical care medicine 2003-01, Vol.31 (1), p.215-220
Hauptverfasser: Asfar, Pierre, Pierrot, Marc, Veal, Nary, Moal, Frédéric, Oberti, Frédéric, Croquet, Vincent, Douay, Olivier, Gallois, Yves, Saumet, Jean-Louis, Alquier, Philippe, Calès, Paul
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container_end_page 220
container_issue 1
container_start_page 215
container_title Critical care medicine
container_volume 31
creator Asfar, Pierre
Pierrot, Marc
Veal, Nary
Moal, Frédéric
Oberti, Frédéric
Croquet, Vincent
Douay, Olivier
Gallois, Yves
Saumet, Jean-Louis
Alquier, Philippe
Calès, Paul
description OBJECTIVEVasopressin has been used to treat arterial hypotension associated with hyperdynamic vasoplegic states, but detrimental effects on splanchnic circulation have been reported. We tested the effects of a low-dose vasopressin analogue, terlipressin (6 μg/kg), on systemic and splanchnic hemodynamics in fluid-challenged endotoxic rats (lipopolysaccharide, 30 mg/kg in 1 hr). DESIGNProspective, randomized, controlled experimental study with repeated measures. SETTINGInvestigational animal laboratory. SUBJECTSA total of 77 rats were divided into five groupsgroup C, control (17 rats); group E, LPS (18 rats); group EF, LPS plus fluid challenge (18 rats); group EFT, LPS plus fluid challenge plus terlipressin (18 rats); and group ET, LPS plus terlipressin (seven rats). INTERVENTIONSRats were anesthetized, mechanically ventilated, and instrumented to measure heart rate, mean arterial pressure, and abdominal aortic and mesenteric vein indexed blood flows; ileal microcirculation was assessed by laser Doppler. After LPS infusion, rats experienced an endotoxic shock and were resuscitated after the allocation group. The fluid challenge was targeted to maintain mean arterial pressure of >90 mm Hg and aortic blood flow at baseline values. MEASUREMENTS AND MAIN RESULTSTerlipressin significantly (p < .05) increased mean arterial pressure without decreasing indexed aortic blood flow and heart rate in the fluid-challenged endotoxic rats (EFT) compared with EF rats and had detrimental effects in hypodynamic endotoxic rats (ET). Fluid challenge significantly (p < .05) increased mesenteric vein blood flow in both the EF and EFT groups, and terlipressin had no detrimental effect on mesenteric blood flow. Terlipressin significantly (p < .05) increased ileal microcirculation in fluid-challenged endotoxic rats (EF and EFT) but not in hypodynamic endotoxic rats (E and ET). CONCLUSIONLow-dose terlipressin in fluid-challenged endotoxic rats improved systemic and splanchnic hemodynamics and improved the ileal microcirculation.
doi_str_mv 10.1097/00003246-200301000-00033
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We tested the effects of a low-dose vasopressin analogue, terlipressin (6 μg/kg), on systemic and splanchnic hemodynamics in fluid-challenged endotoxic rats (lipopolysaccharide, 30 mg/kg in 1 hr). DESIGNProspective, randomized, controlled experimental study with repeated measures. SETTINGInvestigational animal laboratory. SUBJECTSA total of 77 rats were divided into five groupsgroup C, control (17 rats); group E, LPS (18 rats); group EF, LPS plus fluid challenge (18 rats); group EFT, LPS plus fluid challenge plus terlipressin (18 rats); and group ET, LPS plus terlipressin (seven rats). INTERVENTIONSRats were anesthetized, mechanically ventilated, and instrumented to measure heart rate, mean arterial pressure, and abdominal aortic and mesenteric vein indexed blood flows; ileal microcirculation was assessed by laser Doppler. After LPS infusion, rats experienced an endotoxic shock and were resuscitated after the allocation group. The fluid challenge was targeted to maintain mean arterial pressure of &gt;90 mm Hg and aortic blood flow at baseline values. MEASUREMENTS AND MAIN RESULTSTerlipressin significantly (p &lt; .05) increased mean arterial pressure without decreasing indexed aortic blood flow and heart rate in the fluid-challenged endotoxic rats (EFT) compared with EF rats and had detrimental effects in hypodynamic endotoxic rats (ET). Fluid challenge significantly (p &lt; .05) increased mesenteric vein blood flow in both the EF and EFT groups, and terlipressin had no detrimental effect on mesenteric blood flow. Terlipressin significantly (p &lt; .05) increased ileal microcirculation in fluid-challenged endotoxic rats (EF and EFT) but not in hypodynamic endotoxic rats (E and ET). CONCLUSIONLow-dose terlipressin in fluid-challenged endotoxic rats improved systemic and splanchnic hemodynamics and improved the ileal microcirculation.</description><identifier>ISSN: 0090-3493</identifier><identifier>EISSN: 1530-0293</identifier><identifier>DOI: 10.1097/00003246-200301000-00033</identifier><identifier>PMID: 12545018</identifier><identifier>CODEN: CCMDC7</identifier><language>eng</language><publisher>Hagerstown, MD: by the Society of Critical Care Medicine and Lippincott Williams &amp; Wilkins</publisher><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; Animals ; Biological and medical sciences ; Cardiovascular system ; Emergency and intensive care: infection, septic shock ; Hemodynamics - drug effects ; Intensive care medicine ; Lypressin - analogs &amp; derivatives ; Lypressin - pharmacology ; Lypressin - therapeutic use ; Male ; Medical sciences ; Microcirculation ; Pharmacology. Drug treatments ; Random Allocation ; Rats ; Rats, Wistar ; Shock, Septic - drug therapy ; Splanchnic Circulation - drug effects ; Statistics, Nonparametric ; Survival Analysis ; Terlipressin ; Vascular wall ; Vasoconstrictor Agents - pharmacology ; Vasoconstrictor Agents - therapeutic use</subject><ispartof>Critical care medicine, 2003-01, Vol.31 (1), p.215-220</ispartof><rights>2003 by the Society of Critical Care Medicine and Lippincott Williams &amp; Wilkins</rights><rights>2003 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3863-67316c878923b0c5cbe129002f49078b568753330351df29439dd2a091549793</citedby><cites>FETCH-LOGICAL-c3863-67316c878923b0c5cbe129002f49078b568753330351df29439dd2a091549793</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,4024,27923,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=14483877$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12545018$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Asfar, Pierre</creatorcontrib><creatorcontrib>Pierrot, Marc</creatorcontrib><creatorcontrib>Veal, Nary</creatorcontrib><creatorcontrib>Moal, Frédéric</creatorcontrib><creatorcontrib>Oberti, Frédéric</creatorcontrib><creatorcontrib>Croquet, Vincent</creatorcontrib><creatorcontrib>Douay, Olivier</creatorcontrib><creatorcontrib>Gallois, Yves</creatorcontrib><creatorcontrib>Saumet, Jean-Louis</creatorcontrib><creatorcontrib>Alquier, Philippe</creatorcontrib><creatorcontrib>Calès, Paul</creatorcontrib><title>Low-dose terlipressin improves systemic and splanchnic hemodynamics in fluid-challenged endotoxic rats</title><title>Critical care medicine</title><addtitle>Crit Care Med</addtitle><description>OBJECTIVEVasopressin has been used to treat arterial hypotension associated with hyperdynamic vasoplegic states, but detrimental effects on splanchnic circulation have been reported. We tested the effects of a low-dose vasopressin analogue, terlipressin (6 μg/kg), on systemic and splanchnic hemodynamics in fluid-challenged endotoxic rats (lipopolysaccharide, 30 mg/kg in 1 hr). DESIGNProspective, randomized, controlled experimental study with repeated measures. SETTINGInvestigational animal laboratory. SUBJECTSA total of 77 rats were divided into five groupsgroup C, control (17 rats); group E, LPS (18 rats); group EF, LPS plus fluid challenge (18 rats); group EFT, LPS plus fluid challenge plus terlipressin (18 rats); and group ET, LPS plus terlipressin (seven rats). INTERVENTIONSRats were anesthetized, mechanically ventilated, and instrumented to measure heart rate, mean arterial pressure, and abdominal aortic and mesenteric vein indexed blood flows; ileal microcirculation was assessed by laser Doppler. After LPS infusion, rats experienced an endotoxic shock and were resuscitated after the allocation group. The fluid challenge was targeted to maintain mean arterial pressure of &gt;90 mm Hg and aortic blood flow at baseline values. MEASUREMENTS AND MAIN RESULTSTerlipressin significantly (p &lt; .05) increased mean arterial pressure without decreasing indexed aortic blood flow and heart rate in the fluid-challenged endotoxic rats (EFT) compared with EF rats and had detrimental effects in hypodynamic endotoxic rats (ET). Fluid challenge significantly (p &lt; .05) increased mesenteric vein blood flow in both the EF and EFT groups, and terlipressin had no detrimental effect on mesenteric blood flow. Terlipressin significantly (p &lt; .05) increased ileal microcirculation in fluid-challenged endotoxic rats (EF and EFT) but not in hypodynamic endotoxic rats (E and ET). CONCLUSIONLow-dose terlipressin in fluid-challenged endotoxic rats improved systemic and splanchnic hemodynamics and improved the ileal microcirculation.</description><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cardiovascular system</subject><subject>Emergency and intensive care: infection, septic shock</subject><subject>Hemodynamics - drug effects</subject><subject>Intensive care medicine</subject><subject>Lypressin - analogs &amp; derivatives</subject><subject>Lypressin - pharmacology</subject><subject>Lypressin - therapeutic use</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Microcirculation</subject><subject>Pharmacology. Drug treatments</subject><subject>Random Allocation</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Shock, Septic - drug therapy</subject><subject>Splanchnic Circulation - drug effects</subject><subject>Statistics, Nonparametric</subject><subject>Survival Analysis</subject><subject>Terlipressin</subject><subject>Vascular wall</subject><subject>Vasoconstrictor Agents - pharmacology</subject><subject>Vasoconstrictor Agents - therapeutic use</subject><issn>0090-3493</issn><issn>1530-0293</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kcGOFCEQholx446jr2D6ordWoKCBo9mou8kkXvZOGKDtVroZqW7HeftlndE9yaXyw1dQ-SCkYfQ9o0Z9oHUBF13La6WspvZxB56RDZNQAzfwnGwoNbQFYeCavET8TikTUsELcs24FJIyvSH9Lh_bkDE2SyxpPJSIOM7NOB1K_hWxwRMucRp94-bQ4CG52Q9zjUOccjjNrh5hUxv6tI6h9YNLKc7fYmjiHPKSf1e0uAVfkaveJYyvL3VL7j9_ur-5bXdfv9zdfNy1HnQHbaeAdV4rbTjsqZd-Hxk3lPJeGKr0XnZaSQCgIFnouRFgQuCOGiaFUQa25N352jr9zzXiYqcRfUx17JhXtIobJXlVtCX6DPqSEUvs7aGMkysny6h9VGz_Krb_FNs_imvrm8sb636K4anx4rQCby-AQ-9SX6qzEZ84ITRopSonztwxpyoff6T1GIsdokvLYP_3xfAAv_WS1g</recordid><startdate>200301</startdate><enddate>200301</enddate><creator>Asfar, Pierre</creator><creator>Pierrot, Marc</creator><creator>Veal, Nary</creator><creator>Moal, Frédéric</creator><creator>Oberti, Frédéric</creator><creator>Croquet, Vincent</creator><creator>Douay, Olivier</creator><creator>Gallois, Yves</creator><creator>Saumet, Jean-Louis</creator><creator>Alquier, Philippe</creator><creator>Calès, Paul</creator><general>by the Society of Critical Care Medicine and Lippincott Williams &amp; Wilkins</general><general>Lippincott</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><scope>7X8</scope></search><sort><creationdate>200301</creationdate><title>Low-dose terlipressin improves systemic and splanchnic hemodynamics in fluid-challenged endotoxic rats</title><author>Asfar, Pierre ; Pierrot, Marc ; Veal, Nary ; Moal, Frédéric ; Oberti, Frédéric ; Croquet, Vincent ; Douay, Olivier ; Gallois, Yves ; Saumet, Jean-Louis ; Alquier, Philippe ; Calès, Paul</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3863-67316c878923b0c5cbe129002f49078b568753330351df29439dd2a091549793</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Cardiovascular system</topic><topic>Emergency and intensive care: infection, septic shock</topic><topic>Hemodynamics - drug effects</topic><topic>Intensive care medicine</topic><topic>Lypressin - analogs &amp; derivatives</topic><topic>Lypressin - pharmacology</topic><topic>Lypressin - therapeutic use</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Microcirculation</topic><topic>Pharmacology. Drug treatments</topic><topic>Random Allocation</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Shock, Septic - drug therapy</topic><topic>Splanchnic Circulation - drug effects</topic><topic>Statistics, Nonparametric</topic><topic>Survival Analysis</topic><topic>Terlipressin</topic><topic>Vascular wall</topic><topic>Vasoconstrictor Agents - pharmacology</topic><topic>Vasoconstrictor Agents - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Asfar, Pierre</creatorcontrib><creatorcontrib>Pierrot, Marc</creatorcontrib><creatorcontrib>Veal, Nary</creatorcontrib><creatorcontrib>Moal, Frédéric</creatorcontrib><creatorcontrib>Oberti, Frédéric</creatorcontrib><creatorcontrib>Croquet, Vincent</creatorcontrib><creatorcontrib>Douay, Olivier</creatorcontrib><creatorcontrib>Gallois, Yves</creatorcontrib><creatorcontrib>Saumet, Jean-Louis</creatorcontrib><creatorcontrib>Alquier, Philippe</creatorcontrib><creatorcontrib>Calès, Paul</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><collection>MEDLINE - Academic</collection><jtitle>Critical care medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Asfar, Pierre</au><au>Pierrot, Marc</au><au>Veal, Nary</au><au>Moal, Frédéric</au><au>Oberti, Frédéric</au><au>Croquet, Vincent</au><au>Douay, Olivier</au><au>Gallois, Yves</au><au>Saumet, Jean-Louis</au><au>Alquier, Philippe</au><au>Calès, Paul</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Low-dose terlipressin improves systemic and splanchnic hemodynamics in fluid-challenged endotoxic rats</atitle><jtitle>Critical care medicine</jtitle><addtitle>Crit Care Med</addtitle><date>2003-01</date><risdate>2003</risdate><volume>31</volume><issue>1</issue><spage>215</spage><epage>220</epage><pages>215-220</pages><issn>0090-3493</issn><eissn>1530-0293</eissn><coden>CCMDC7</coden><abstract>OBJECTIVEVasopressin has been used to treat arterial hypotension associated with hyperdynamic vasoplegic states, but detrimental effects on splanchnic circulation have been reported. We tested the effects of a low-dose vasopressin analogue, terlipressin (6 μg/kg), on systemic and splanchnic hemodynamics in fluid-challenged endotoxic rats (lipopolysaccharide, 30 mg/kg in 1 hr). DESIGNProspective, randomized, controlled experimental study with repeated measures. SETTINGInvestigational animal laboratory. SUBJECTSA total of 77 rats were divided into five groupsgroup C, control (17 rats); group E, LPS (18 rats); group EF, LPS plus fluid challenge (18 rats); group EFT, LPS plus fluid challenge plus terlipressin (18 rats); and group ET, LPS plus terlipressin (seven rats). INTERVENTIONSRats were anesthetized, mechanically ventilated, and instrumented to measure heart rate, mean arterial pressure, and abdominal aortic and mesenteric vein indexed blood flows; ileal microcirculation was assessed by laser Doppler. After LPS infusion, rats experienced an endotoxic shock and were resuscitated after the allocation group. The fluid challenge was targeted to maintain mean arterial pressure of &gt;90 mm Hg and aortic blood flow at baseline values. MEASUREMENTS AND MAIN RESULTSTerlipressin significantly (p &lt; .05) increased mean arterial pressure without decreasing indexed aortic blood flow and heart rate in the fluid-challenged endotoxic rats (EFT) compared with EF rats and had detrimental effects in hypodynamic endotoxic rats (ET). Fluid challenge significantly (p &lt; .05) increased mesenteric vein blood flow in both the EF and EFT groups, and terlipressin had no detrimental effect on mesenteric blood flow. Terlipressin significantly (p &lt; .05) increased ileal microcirculation in fluid-challenged endotoxic rats (EF and EFT) but not in hypodynamic endotoxic rats (E and ET). CONCLUSIONLow-dose terlipressin in fluid-challenged endotoxic rats improved systemic and splanchnic hemodynamics and improved the ileal microcirculation.</abstract><cop>Hagerstown, MD</cop><pub>by the Society of Critical Care Medicine and Lippincott Williams &amp; Wilkins</pub><pmid>12545018</pmid><doi>10.1097/00003246-200301000-00033</doi><tpages>6</tpages></addata></record>
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subjects Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
Animals
Biological and medical sciences
Cardiovascular system
Emergency and intensive care: infection, septic shock
Hemodynamics - drug effects
Intensive care medicine
Lypressin - analogs & derivatives
Lypressin - pharmacology
Lypressin - therapeutic use
Male
Medical sciences
Microcirculation
Pharmacology. Drug treatments
Random Allocation
Rats
Rats, Wistar
Shock, Septic - drug therapy
Splanchnic Circulation - drug effects
Statistics, Nonparametric
Survival Analysis
Terlipressin
Vascular wall
Vasoconstrictor Agents - pharmacology
Vasoconstrictor Agents - therapeutic use
title Low-dose terlipressin improves systemic and splanchnic hemodynamics in fluid-challenged endotoxic rats
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